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Clinical Trial Results:
A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Patients with Diabetic Macular Edema (YOSEMITE)

Summary
EudraCT number	2017-005104-10
Trial protocol	SK BG DE HU AT ES IT
Global end of trial date	03 Sep 2021

Results information
Results version number	v1(current)
This version publication date	07 Sep 2022
First version publication date	07 Sep 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GR40349

ISRCTN number

US NCT number

NCT03622580

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche, Ltd.

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

F. Hoffmann-La Roche, Ltd., F. Hoffmann-La Roche, Ltd., +41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche, Ltd., F. Hoffmann-La Roche, Ltd., +41 616878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

03 Sep 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

20 Oct 2020

Global end of trial reached?

Yes

Global end of trial date

03 Sep 2021

Was the trial ended prematurely?

Main objective of the trial

The main objective of the trial was to evaluate the efficacy of intravitreal (IVT) injections of faricimab on best-corrected visual acuity (BCVA) outcomes.

Protection of trial subjects

This study was conducted in full conformance with the ICH E6 guideline for Good Clinical Practice and the principles of the Declaration of Helsinki, or the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual. All participants were required to read and sign an informed consent form prior to participation in the study.

Background therapy

Evidence for comparator

Actual start date of recruitment

05 Sep 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 9

Country: Number of subjects enrolled

Bulgaria: 28

Country: Number of subjects enrolled

France: 6

Country: Number of subjects enrolled

Germany: 5

Country: Number of subjects enrolled

Hungary: 52

Country: Number of subjects enrolled

Israel: 41

Country: Number of subjects enrolled

Italy: 18

Country: Number of subjects enrolled

Japan: 60

Country: Number of subjects enrolled

Mexico: 25

Country: Number of subjects enrolled

Peru: 15

Country: Number of subjects enrolled

Poland: 101

Country: Number of subjects enrolled

Russian Federation: 15

Country: Number of subjects enrolled

Slovakia: 29

Country: Number of subjects enrolled

Spain: 27

Country: Number of subjects enrolled

Turkey: 6

Country: Number of subjects enrolled

United States: 503

Worldwide total number of subjects

940

EEA total number of subjects

275

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

537

From 65 to 84 years

401

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 1532 patients were screened, and 592 patients failed screening due to notmeeting the inclusion criteria. A total of 940 patients with DME were randomized 1:1:1 using a stratified permuted-block randomization scheme into the study: 315 to Arm A: Faricimab 6 mg Q8W, 313 to Arm B: Faricimab 6 mg PTI, and 312 to Arm C: Aflibercept 2 mg Q8W.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst, Assessor

Are arms mutually exclusive

Yes

A: Faricimab 6 mg Q8W

Arm description

Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.

Arm type

Experimental

Investigational medicinal product name

Faricimab

Investigational medicinal product code

RO6867461

Other name

Vabysmo™, VA2, Humanized anti-VEGF-A anti-Ang-2 bispecific Antibody

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

B: Faricimab 6 mg PTI

Arm description

Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.

Arm type

Experimental

Investigational medicinal product name

Faricimab

Investigational medicinal product code

RO6867461

Other name

Vabysmo™, VA2, Humanized anti-VEGF-A anti-Ang-2 bispecific Antibody

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

C: Aflibercept 2 mg Q8W

Arm description

Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.

Arm type

Active comparator

Investigational medicinal product name

Aflibercept

Investigational medicinal product code

Other name

Eylea

Pharmaceutical forms

Solution for injection

Routes of administration

Intravitreal use

Dosage and administration details

Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96.

Number of subjects in period 1	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Started	315	313	312
Received at Least One Dose of Study Drug	313	313	311
Completed up to Week 56	291	289	292
Completed	263	269	260
Not completed	52	44	52
Consent withdrawn by subject	12	7	19
Physician decision	3	-	1
Adverse event, non-fatal	6	6	5
Death	16	21	13
Not Specified	2	-	3
Pregnancy	-	1	-
Lost to follow-up	12	9	9
Protocol deviation	1	-	1
Lack of efficacy	-	-	1

Baseline characteristics

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Reporting group title

A: Faricimab 6 mg Q8W

Reporting group description

Reporting group title

B: Faricimab 6 mg PTI

Reporting group description

Reporting group title

C: Aflibercept 2 mg Q8W

Reporting group description

Reporting group values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W	Total
Number of subjects	315	313	312	940
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	188	169	180	537
From 65-84 years	126	143	132	401
85 years and over	1	1	0	2
Age Continuous
Units: Years
arithmetic mean (standard deviation)	61.6 ( 9.5 )	62.8 ( 10.0 )	62.2 ( 9.6 )	-
Sex: Female, Male
Units: Participants
Female	128	116	134	378
Male	187	197	178	562
Number of Participants by Previous Treatment Status with Intravitreal Anti-VEGF Agents
The Treatment-Naive Population was defined as all participants randomized in the study who had not received any intravitreal (IVT) anti-VEGF agents in the study eye prior to randomization.
Units: Subjects
Treatment-Naive	238	245	242	725
Previously Treated	77	68	70	215
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	6	5	7	18
Asian	31	26	27	84
Native Hawaiian or Other Pacific Islander	2	0	3	5
Black or African American	22	25	12	59
White	241	240	253	734
More than one race	0	1	0	1
Unknown or Not Reported	13	16	10	39
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	37	40	37	114
Not Hispanic or Latino	273	268	272	813
Unknown or Not Reported	5	5	3	13
Region of Enrollment
Units: Subjects
United States and Canada	167	168	168	503
Asia	21	19	20	60
Rest of the World	127	126	124	377
Number of Participants by the Eye Chosen as the Study Eye (Left or Right)
Units: Subjects
Left Eye	150	172	151	473
Right Eye	165	141	161	467
Number of Participants by the Baseline BCVA Letter Score Categories in the Study Eye
Best corrected visual acuity (BCVA) was measured at a starting test distance of 4 meters using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R). The BCVA letter score ranges from 0 to 100 (best score attainable), with a higher score indicating better visual acuity.
Units: Subjects
≤38 Letters	15	12	12	39
39 to 63 Letters	132	126	132	390
≥64 Letters	168	175	168	511
Missing/Invalid BCVA	0	0	0	0
Number of Participants by Baseline Diabetic Retinopathy Severity (DRS) Status in the Study Eye
The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center.
Units: Subjects
1 - Diabetic Retinopathy (DR) Absent	2	3	4	9
2 - DR Questionable / Microaneurysms Only	4	6	10	20
3 - Mild Non-Proliferative DR (NPDR)	84	92	83	259
4 - Moderate NPDR	84	86	85	255
5 - Moderately Severe NPDR	67	59	54	180
6 - Severe NPDR	46	40	49	135
7 - Mild Proliferative Diabetic Retinopathy (PDR)	16	11	9	36
8 - Moderate PDR	6	9	7	22
9 - High Risk PDR (DRS Level 71)	0	1	2	3
10 - High Risk PDR (DRS Level 75)	0	0	0	0
11 - Advanced PDR (DRS Level 81)	0	0	0	0
12 - Advanced PDR (DRS Level 85)	0	0	0	0
Cannot Grade	4	5	7	16
Missing	2	1	2	5
Baseline Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye
Best corrected visual acuity (BCVA) was measured at a starting test distance of 4 meters using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R). The BCVA letter score ranges from 0 to 100 (best score attainable), with a higher score indicating better visual acuity.
Units: ETDRS Letters
arithmetic mean (standard deviation)	62.0 ( 9.9 )	61.9 ( 10.2 )	62.2 ( 9.5 )	-
Baseline Central Subfield Thickness in the Study Eye
Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center.
Units: microns
arithmetic mean (standard deviation)	492.3 ( 135.8 )	485.8 ( 130.8 )	484.5 ( 131.1 )	-

Subject analysis set title

A: Faricimab 6 mg Q8W, TN Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

The treatment-naive (TN) population was defined as all patients randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.

Subject analysis set title

B: Faricimab 6 mg PTI, TN Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

The treatment-naive (TN) population was defined as all patients randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.

Subject analysis set title

C: Aflibercept 2 mg Q8W, TN Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

The treatment-naive (TN) population was defined as all patients randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.

Subject analysis sets values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects	238	245	242
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
85 years and over
Age Continuous
Units: Years
arithmetic mean (standard deviation)	61.0 ( 9.6 )	62.5 ( 10.3 )	62.2 ( 9.9 )
Sex: Female, Male
Units: Participants
Female	93	91	108
Male	145	154	134
Number of Participants by Previous Treatment Status with Intravitreal Anti-VEGF Agents
The Treatment-Naive Population was defined as all participants randomized in the study who had not received any intravitreal (IVT) anti-VEGF agents in the study eye prior to randomization.
Units: Subjects
Treatment-Naive
Previously Treated
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	4	3	6
Asian	21	18	20
Native Hawaiian or Other Pacific Islander	2	0	2
Black or African American	17	24	9
White	181	186	196
More than one race	0	1	0
Unknown or Not Reported	13	13	9
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	31	32	31
Not Hispanic or Latino	202	210	208
Unknown or Not Reported	5	3	3
Region of Enrollment
Units: Subjects
United States and Canada	130	134	135
Asia	14	14	15
Rest of the World	94	97	92
Number of Participants by the Eye Chosen as the Study Eye (Left or Right)
Units: Subjects
Left Eye	117	130	117
Right Eye	121	115	125
Number of Participants by the Baseline BCVA Letter Score Categories in the Study Eye
Best corrected visual acuity (BCVA) was measured at a starting test distance of 4 meters using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R). The BCVA letter score ranges from 0 to 100 (best score attainable), with a higher score indicating better visual acuity.
Units: Subjects
≤38 Letters	10	11	8
39 to 63 Letters	98	95	100
≥64 Letters	130	139	134
Missing/Invalid BCVA	0	0	0
Number of Participants by Baseline Diabetic Retinopathy Severity (DRS) Status in the Study Eye
The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center.
Units: Subjects
1 - Diabetic Retinopathy (DR) Absent	2	3	2
2 - DR Questionable / Microaneurysms Only	1	4	4
3 - Mild Non-Proliferative DR (NPDR)	65	66	57
4 - Moderate NPDR	56	58	65
5 - Moderately Severe NPDR	50	52	48
6 - Severe NPDR	40	38	46
7 - Mild Proliferative Diabetic Retinopathy (PDR)	13	9	6
8 - Moderate PDR	6	9	6
9 - High Risk PDR (DRS Level 71)	0	0	2
10 - High Risk PDR (DRS Level 75)	0	0	0
11 - Advanced PDR (DRS Level 81)	0	0	0
12 - Advanced PDR (DRS Level 85)	0	0	0
Cannot Grade	4	5	5
Missing	1	1	1
Baseline Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye
Best corrected visual acuity (BCVA) was measured at a starting test distance of 4 meters using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R). The BCVA letter score ranges from 0 to 100 (best score attainable), with a higher score indicating better visual acuity.
Units: ETDRS Letters
arithmetic mean (standard deviation)	62.3 ( 9.9 )	61.8 ( 10.7 )	62.6 ( 9.2 )
Baseline Central Subfield Thickness in the Study Eye
Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center.
Units: microns
arithmetic mean (standard deviation)	488.8 ( 136.8 )	483.5 ( 127.3 )	486.8 ( 130.4 )

End points

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Reporting group title

A: Faricimab 6 mg Q8W

Reporting group description

Reporting group title

B: Faricimab 6 mg PTI

Reporting group description

Reporting group title

C: Aflibercept 2 mg Q8W

Reporting group description

Subject analysis set title

A: Faricimab 6 mg Q8W, TN Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

B: Faricimab 6 mg PTI, TN Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

The treatment-naive (TN) population was defined as all patients randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.

Subject analysis set title

C: Aflibercept 2 mg Q8W, TN Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

The treatment-naive (TN) population was defined as all patients randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.

Primary: Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

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End point title

Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded. 97.5% CI is a rounding of 97.52% CI.

End point type

Primary

End point timeframe

From Baseline through Week 56

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	315	313	312	238	245	242
Units: ETDRS Letters
arithmetic mean (confidence interval 97.5%)	10.7 (9.4 to 12.0)	11.6 (10.3 to 12.9)	10.9 (9.6 to 12.2)	10.6 (9.1 to 12.1)	11.4 (9.9 to 12.8)	11.3 (9.8 to 12.8)

Non-Inferiority: Arm A vs. Arm C, ITT

Statistical analysis description

Three hypotheses were tested in order for each faricimab arm (Q8W or PTI) separately against the aflibercept arm using a graph-based testing procedure. The analysis presented here is for the non-inferiority of Arm A: Faricimab 6 mg Q8W compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

627

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

Method

Parameter type

Adjusted mean difference

Point estimate

-0.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

-2

upper limit

1.6

Variability estimate

Standard error of the mean

Dispersion value

0.79

Notes
[1] - If the lower bound of the two-sided 97.52% confidence interval for the difference in adjusted means for the faricimab 6 mg Q8W and the active comparator (aflibercept 2 mg Q8W) arms was greater than –4 letters, then faricimab 6 mg Q8W was considered non-inferior to aflibercept 2 mg Q8W. Non-inferiority was tested one-sided at a significance level of α = 0.0248.

Non-Inferiority: Arm B vs. Arm C, ITT

Statistical analysis description

Three hypotheses were tested in order for each faricimab arm (Q8W or PTI) separately against the aflibercept arm using a graph-based testing procedure. The analysis presented here is for the non-inferiority of Arm B: Faricimab 6 mg PTI compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

625

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Parameter type

Adjusted mean difference

Point estimate

0.7

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1.1

upper limit

2.5

Variability estimate

Standard error of the mean

Dispersion value

0.79

Notes
[2] - If the lower bound of the two-sided 97.52% confidence interval for the difference in adjusted means for the faricimab 6 mg PTI and the active comparator (aflibercept 2 mg Q8W) arms was greater than –4 letters, then faricimab 6 mg PTI was considered non-inferior to aflibercept 2 mg Q8W. Non-inferiority was tested one-sided at a significance level of α = 0.0248.

Superiority: Arm A vs. Arm C, TN

Statistical analysis description

Three hypotheses were tested in order for each faricimab arm (Q8W or PTI) separately against the aflibercept arm using a graph-based testing procedure. The analysis presented here is for the superiority of Arm A: Faricimab 6 mg Q8W compared with Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

480

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4699 ^[3]

Method

Mixed Model for Repeated Measures

Parameter type

Adjusted mean difference

Point estimate

-0.7

Confidence interval

level

97.5%

sides

2-sided

lower limit

-2.8

upper limit

1.4

Variability estimate

Standard error of the mean

Dispersion value

0.95

Notes
[3] - Tested at an overall significance level of α = 0.0248.

Superiority: Arm B vs. Arm C, TN

Statistical analysis description

Three hypotheses were tested in order for each faricimab arm (Q8W or PTI) separately against the aflibercept arm using a graph-based testing procedure. The analysis presented here is for the superiority of Arm B: Faricimab 6 mg PTI compared with Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

487

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.965 ^[4]

Method

Mixed Model for Repeated Measures

Parameter type

Adjusted mean difference

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-2.1

upper limit

2.2

Variability estimate

Standard error of the mean

Dispersion value

0.94

Notes
[4] - Tested at an overall significance level of α = 0.0248.

Superiority: Arm A vs. Arm C, ITT

Statistical analysis description

Three hypotheses were tested in order for each faricimab arm (Q8W or PTI) separately against the aflibercept arm using a graph-based testing procedure. The analysis presented here is for the superiority of Arm A: Faricimab 6 mg Q8W compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

627

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7967 ^[5]

Method

Mixed Model for Repeated Measures

Parameter type

Adjusted mean difference

Point estimate

-0.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

-2

upper limit

1.6

Variability estimate

Standard error of the mean

Dispersion value

0.79

Notes
[5] - Tested at an overall significance level of α = 0.0248.

Superiority: Arm B vs. Arm C, ITT

Statistical analysis description

Three hypotheses were tested in order for each faricimab arm (Q8W or PTI) separately against the aflibercept arm using a graph-based testing procedure. The analysis presented here is for the superiority of Arm B: Faricimab 6 mg PTI compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

625

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3772 ^[6]

Method

Mixed Model for Repeated Measures

Parameter type

Adjusted mean difference

Point estimate

0.7

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1.1

upper limit

2.5

Variability estimate

Standard error of the mean

Dispersion value

0.79

Notes
[6] - Tested at an overall significance level of α = 0.0248.

Secondary: Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale at Week 52, ITT and Treatment-Naive Populations

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End point title

Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale at Week 52, ITT and Treatment-Naive Populations

End point description

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 97.5% confidence interval (CI) is a rounding of 97.52% CI.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	237	242	229	173	187	179
Units: Percentage of participants
number (confidence interval 97.5%)	46.0 (38.8 to 53.1)	42.5 (35.5 to 49.5)	35.8 (29.1 to 42.5)	49.7 (41.2 to 58.2)	47.6 (39.5 to 55.8)	42.5 (34.4 to 50.6)

Non-Inferiority: Arm A vs. Arm C, ITT

Statistical analysis description

The analysis presented here is for the non-inferiority of Arm A: Faricimab 6 mg Q8W compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

466

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

10.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.3

upper limit

Notes
[7] - If the lower bound of the two-sided 97.52% confidence interval for the difference in CMH weighted percentages of participants for the faricimab 6 mg Q8W and the active comparator (aflibercept 2 mg Q8W) arms was greater than –10%, then faricimab 6 mg Q8W was considered non-inferior to aflibercept 2 mg Q8W.

Non-Inferiority: Arm B vs. Arm C, ITT

Statistical analysis description

The analysis presented here is for the non-inferiority of Arm B: Faricimab 6 mg PTI compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

471

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

6.1

Confidence interval

level

97.5%

sides

2-sided

lower limit

-3.6

upper limit

15.8

Notes
[8] - If the lower bound of the two-sided 97.52% confidence interval for the difference in CMH weighted percentages of participants for the faricimab 6 mg PTI and the active comparator (aflibercept 2 mg Q8W) arms was greater than –10%, then faricimab 6 mg PTI was considered non-inferior to aflibercept 2 mg Q8W.

Superiority: Arm A vs. Arm C, TN

Statistical analysis description

The analysis presented here is for the superiority of Arm A: Faricimab 6 mg Q8W compared with Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

352

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1761 ^[9]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in CMH Weighted Percentage

Point estimate

7.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

-4.6

upper limit

18.9

Notes
[9] - Tested at an overall significance level of α = 0.0248.

Superiority: Arm B vs. Arm C, TN

Statistical analysis description

The analysis presented here is for the superiority of Arm B: Faricimab 6 mg PTI compared with Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

366

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3539 ^[10]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in CMH Weighted Percentage

Point estimate

4.8

Confidence interval

level

97.5%

sides

2-sided

lower limit

-6.7

upper limit

16.3

Notes
[10] - Tested at an overall significance level of α = 0.0248.

Superiority: Arm A vs. Arm C, ITT

Statistical analysis description

The analysis presented here is for the superiority of Arm A: Faricimab 6 mg Q8W compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

466

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0237 ^[11]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in CMH Weighted Percentage

Point estimate

10.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.3

upper limit

Notes
[11] - Tested at an overall significance level of α = 0.0248.

Superiority: Arm B vs. Arm C, ITT

Statistical analysis description

The analysis presented here is for the superiority of Arm B: Faricimab 6 mg PTI compared with Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

471

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1677 ^[12]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in CMH Weighted Percentage

Point estimate

6.1

Confidence interval

level

97.5%

sides

2-sided

lower limit

-3.6

upper limit

15.8

Notes
[12] - Tested at an overall significance level of α = 0.0248.

Secondary: Change from Baseline in BCVA in the Study Eye Over Time, ITT Population

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End point title

Change from Baseline in BCVA in the Study Eye Over Time, ITT Population

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: ETDRS Letters
arithmetic mean (confidence interval 95%)
Week 4	5.5 (4.8 to 6.3)	6.7 (6.0 to 7.4)	6.5 (5.8 to 7.2)
Week 8	7.2 (6.4 to 7.9)	8.2 (7.4 to 9.0)	8.1 (7.3 to 8.8)
Week 12	8.2 (7.4 to 9.0)	9.2 (8.4 to 10.0)	9.1 (8.3 to 9.9)
Week 16	9.1 (8.2 to 9.9)	10.0 (9.2 to 10.8)	9.7 (8.8 to 10.5)
Week 20	9.6 (8.7 to 10.5)	9.9 (9.0 to 10.8)	9.8 (8.9 to 10.7)
Week 24	10.2 (9.3 to 11.1)	11.3 (10.4 to 12.2)	9.4 (8.5 to 10.3)
Week 28	9.5 (8.6 to 10.5)	11.0 (10.0 to 11.9)	10.5 (9.6 to 11.5)
Week 32	10.2 (9.2 to 11.2)	10.9 (9.9 to 11.9)	10.2 (9.2 to 11.2)
Week 36	10.1 (9.1 to 11.1)	11.7 (10.7 to 12.8)	10.4 (9.4 to 11.4)
Week 40	10.2 (9.1 to 11.2)	11.4 (10.3 to 12.5)	10.3 (9.2 to 11.4)
Week 44	9.9 (8.8 to 11.0)	11.4 (10.3 to 12.5)	10.7 (9.6 to 11.9)
Week 48	10.5 (9.4 to 11.6)	11.4 (10.3 to 12.5)	10.8 (9.7 to 11.9)
Week 52	9.9 (8.7 to 11.1)	11.0 (9.8 to 12.2)	10.9 (9.7 to 12.2)
Week 56	10.8 (9.7 to 12.0)	11.6 (10.4 to 12.8)	10.6 (9.4 to 11.8)
Week 60	10.3 (9.1 to 11.5)	12.0 (10.8 to 13.1)	11.3 (10.1 to 12.5)
Week 64	10.7 (9.5 to 12.0)	11.5 (10.3 to 12.7)	10.8 (9.6 to 12.0)
Week 68	10.2 (8.9 to 11.5)	11.4 (10.1 to 12.6)	11.3 (10.0 to 12.5)
Week 72	10.4 (9.1 to 11.7)	11.3 (10.0 to 12.6)	10.7 (9.4 to 12.0)
Week 76	10.2 (8.8 to 11.6)	11.5 (10.1 to 12.9)	11.0 (9.6 to 12.4)
Week 80	10.9 (9.5 to 12.2)	11.1 (9.8 to 12.4)	10.9 (9.6 to 12.2)
Week 84	9.9 (8.6 to 11.2)	11.5 (10.2 to 12.8)	11.8 (10.5 to 13.1)
Week 88	9.8 (8.4 to 11.2)	10.9 (9.5 to 12.3)	11.0 (9.6 to 12.4)
Week 92	10.5 (9.1 to 11.9)	11.2 (9.9 to 12.6)	11.5 (10.1 to 12.9)
Week 96	11.1 (9.7 to 12.6)	10.6 (9.2 to 12.0)	11.1 (9.7 to 12.5)
Week 100	10.5 (9.1 to 12.0)	10.4 (9.0 to 11.8)	11.6 (10.1 to 13.1)

No statistical analyses for this end point

Secondary: Change from Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population

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End point title

Change from Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population

End point description

Best-Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline BCVA (continuous), baseline BCVA (<64 vs. ≥64 letters), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: ETDRS Letters
arithmetic mean (confidence interval 95%)
Week 4	5.8 (5.0 to 6.7)	6.8 (6.0 to 7.6)	6.9 (6.1 to 7.7)
Week 8	7.2 (6.3 to 8.1)	8.3 (7.4 to 9.2)	8.7 (7.8 to 9.5)
Week 12	8.5 (7.6 to 9.4)	9.3 (8.4 to 10.2)	9.6 (8.7 to 10.5)
Week 16	9.3 (8.4 to 10.3)	10.0 (9.1 to 10.9)	10.1 (9.2 to 11.1)
Week 20	9.7 (8.7 to 10.8)	9.7 (8.6 to 10.7)	10.3 (9.3 to 11.4)
Week 24	10.5 (9.4 to 11.5)	11.2 (10.2 to 12.2)	9.8 (8.7 to 10.8)
Week 28	9.6 (8.5 to 10.7)	11.0 (9.9 to 12.1)	11.0 (9.9 to 12.1)
Week 32	10.3 (9.1 to 11.5)	10.9 (9.8 to 12.1)	10.6 (9.5 to 11.8)
Week 36	10.3 (9.1 to 11.6)	11.9 (10.7 to 13.1)	10.6 (9.4 to 11.8)
Week 40	10.0 (8.7 to 11.3)	11.4 (10.1 to 12.7)	10.7 (9.4 to 12.1)
Week 44	10.1 (8.8 to 11.4)	11.4 (10.1 to 12.7)	11.3 (10.0 to 12.6)
Week 48	10.3 (9.0 to 11.7)	11.0 (9.7 to 12.4)	11.2 (9.8 to 12.5)
Week 52	9.6 (8.2 to 11.1)	10.7 (9.3 to 12.2)	11.3 (9.9 to 12.8)
Week 56	10.9 (9.5 to 12.3)	11.5 (10.1 to 12.8)	11.0 (9.6 to 12.4)
Week 60	10.1 (8.7 to 11.6)	12.0 (10.6 to 13.4)	11.6 (10.2 to 13.0)
Week 64	10.6 (9.1 to 12.1)	11.5 (10.0 to 13.0)	11.0 (9.5 to 12.4)
Week 68	10.3 (8.8 to 11.8)	11.3 (9.8 to 12.8)	11.4 (9.9 to 12.9)
Week 72	10.2 (8.6 to 11.7)	11.3 (9.8 to 12.8)	10.8 (9.3 to 12.4)
Week 76	9.9 (8.2 to 11.6)	11.4 (9.7 to 13.0)	10.8 (9.2 to 12.5)
Week 80	10.6 (9.0 to 12.2)	11.0 (9.4 to 12.6)	11.1 (9.6 to 12.7)
Week 84	9.6 (8.0 to 11.1)	11.6 (10.0 to 13.1)	11.9 (10.3 to 13.4)
Week 88	9.4 (7.7 to 11.1)	10.8 (9.1 to 12.5)	10.9 (9.2 to 12.6)
Week 92	10.1 (8.4 to 11.7)	11.2 (9.5 to 12.8)	11.6 (10.0 to 13.3)
Week 96	11.1 (9.4 to 12.8)	10.5 (8.9 to 12.1)	11.4 (9.7 to 13.0)
Week 100	10.5 (8.8 to 12.3)	10.5 (8.8 to 12.1)	11.7 (10.0 to 13.4)

No statistical analyses for this end point

Secondary: Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population

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End point title

Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population

End point description

BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, average of Weeks 48, 52, and 56

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	271	276	276
Units: Percentage of participants
number (confidence interval 95%)
Gaining ≥15 Letters	29.2 (23.9 to 34.5)	35.5 (30.1 to 40.9)	31.8 (26.6 to 37.0)
Gaining ≥10 Letters	57.2 (51.3 to 63.1)	58.3 (52.6 to 64.0)	57.6 (51.8 to 63.4)
Gaining ≥5 Letters	78.9 (74.1 to 83.8)	79.6 (74.9 to 84.3)	81.4 (76.9 to 86.0)
Gaining ≥0 Letters	91.5 (88.1 to 94.8)	94.5 (91.8 to 97.2)	91.4 (88.1 to 94.6)

Gaining ≥15 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥15 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

547

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-10

upper limit

4.9

Gaining ≥15 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥15 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

11.1

Gaining ≥10 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥10 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

547

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-8.6

upper limit

7.9

Gaining ≥10 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥10 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

8.8

Gaining ≥5 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥5 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-8.5

upper limit

4.5

Gaining ≥5 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥5 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

547

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-9.1

upper limit

4.1

Gaining ≥0 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥0 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

547

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.6

upper limit

4.8

Gaining ≥0 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥0 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

7.5

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 310,308,306)	7.7 (4.8 to 10.7)	13.0 (9.4 to 16.6)	11.4 (8.0 to 14.9)
Week 8 (n = 309,308,304)	13.4 (9.6 to 17.1)	18.8 (14.8 to 22.9)	16.7 (12.7 to 20.7)
Week 12 (n = 305,303,302)	14.9 (11.0 to 18.9)	23.1 (18.6 to 27.5)	22.1 (17.6 to 26.5)
Week 16 (n = 296,296,299)	20.4 (15.9 to 24.9)	27.8 (22.9 to 32.7)	22.2 (17.7 to 26.8)
Week 20 (n = 294,292,296)	25.6 (20.8 to 30.5)	28.4 (23.4 to 33.4)	24.0 (19.4 to 28.6)
Week 24 (n = 292,293,294)	26.8 (21.8 to 31.8)	34.2 (29.0 to 39.3)	25.7 (21.0 to 30.5)
Week 28 (n = 283,287,284)	23.5 (18.6 to 28.4)	31.2 (26.2 to 36.3)	29.2 (24.3 to 34.2)
Week 32 (n = 267,268,275)	28.5 (23.1 to 33.8)	36.2 (30.7 to 41.7)	25.8 (21.0 to 30.7)
Week 36 (n = 268,268,268)	24.4 (19.3 to 29.5)	40.2 (34.6 to 45.8)	32.5 (27.1 to 37.9)
Week 40 (n = 275,269,263)	29.7 (24.3 to 35.1)	37.1 (31.6 to 42.7)	30.3 (24.9 to 35.6)
Week 44 (n = 268,269,266)	29.2 (23.8 to 34.6)	37.1 (31.7 to 42.6)	34.9 (29.4 to 40.4)
Week 48 (n = 264,266,266)	31.7 (26.1 to 37.2)	39.6 (33.9 to 45.3)	34.0 (28.7 to 39.3)
Week 52 (n = 264,267,253)	31.2 (25.7 to 36.8)	37.2 (31.7 to 42.7)	36.0 (30.3 to 41.6)
Week 56 (n = 260,263,256)	38.1 (32.3 to 43.9)	38.4 (32.7 to 44.0)	31.5 (26.1 to 36.9)
Week 60 (n = 270,261,261)	34.4 (28.8 to 40.0)	41.3 (35.5 to 47.1)	35.9 (30.3 to 41.4)
Week 64 (n = 259,263,263)	37.5 (31.7 to 43.4)	41.4 (35.8 to 47.1)	34.8 (29.1 to 40.5)
Week 68 (n = 251,257,253)	37.1 (31.4 to 42.9)	43.7 (37.9 to 49.6)	37.1 (31.4 to 42.8)
Week 72 (n = 253,257,251)	34.8 (29.1 to 40.6)	38.2 (32.6 to 43.8)	35.2 (29.5 to 41.0)
Week 76 (n = 247,253,251)	36.6 (30.7 to 42.6)	44.1 (38.4 to 49.9)	37.2 (31.3 to 43.1)
Week 80 (n = 247,259,251)	39.3 (33.4 to 45.3)	42.1 (36.5 to 47.8)	36.9 (31.1 to 42.6)
Week 84 (n = 248,260,252)	40.6 (34.5 to 46.6)	41.5 (35.8 to 47.2)	38.8 (32.9 to 44.6)
Week 88 (n = 245,256,247)	39.2 (33.2 to 45.2)	39.8 (34.2 to 45.4)	35.9 (30.1 to 41.6)
Week 92 (n = 248,258,248)	39.7 (33.8 to 45.7)	41.0 (35.3 to 46.6)	38.8 (33.0 to 44.7)
Week 96 (n = 242,259,245)	41.3 (35.1 to 47.4)	40.2 (34.5 to 45.8)	38.8 (32.9 to 44.7)
Week 100 (n = 254,258,247)	40.2 (34.2 to 46.1)	40.3 (34.7 to 46.0)	40.9 (34.9 to 46.9)

No statistical analyses for this end point

Secondary: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 310,308,306)	23.9 (19.2 to 28.6)	31.1 (26.2 to 36.1)	27.1 (22.2 to 32.0)
Week 8 (n = 309,308,304)	30.8 (25.7 to 35.9)	37.1 (31.8 to 42.3)	41.0 (35.6 to 46.4)
Week 12 (n = 305,303,302)	35.5 (30.2 to 40.8)	47.5 (42.0 to 53.0)	46.2 (40.7 to 51.7)
Week 16 (n = 296,296,299)	43.7 (38.0 to 49.3)	48.4 (42.8 to 54.0)	49.7 (44.1 to 55.3)
Week 20 (n = 294,292,296)	45.6 (40.0 to 51.3)	53.1 (47.6 to 58.6)	50.3 (44.7 to 56.0)
Week 24 (n = 292,293,294)	55.6 (50.0 to 61.2)	58.6 (53.2 to 64.1)	48.2 (42.6 to 53.9)
Week 28 (n = 283,287,284)	55.6 (49.9 to 61.3)	57.0 (51.4 to 62.6)	57.2 (51.6 to 62.9)
Week 32 (n = 267,268,275)	56.7 (50.9 to 62.6)	58.5 (52.8 to 64.2)	53.1 (47.3 to 58.8)
Week 36 (n = 268,268,268)	55.6 (49.7 to 61.5)	65.5 (60.0 to 71.1)	55.7 (49.9 to 61.6)
Week 40 (n = 275,269,263)	55.7 (49.8 to 61.5)	60.0 (54.2 to 65.8)	53.2 (47.2 to 59.2)
Week 44 (n = 268,269,266)	55.1 (49.3 to 61.0)	60.5 (54.7 to 66.2)	57.2 (51.3 to 63.2)
Week 48 (n = 264,266,266)	57.0 (51.0 to 62.9)	60.2 (54.5 to 65.9)	61.7 (55.9 to 67.4)
Week 52 (n = 264,267,253)	59.9 (54.0 to 65.8)	59.5 (53.8 to 65.2)	60.2 (54.3 to 66.2)
Week 56 (n = 260,263,256)	63.5 (57.7 to 69.4)	62.6 (56.9 to 68.3)	59.0 (53.0 to 64.9)
Week 60 (n = 270,261,261)	59.4 (53.5 to 65.2)	62.6 (56.9 to 68.3)	60.7 (54.9 to 66.5)
Week 64 (n = 259,263,263)	64.9 (59.2 to 70.7)	60.0 (54.3 to 65.7)	59.6 (53.8 to 65.5)
Week 68 (n = 251,257,253)	60.1 (54.2 to 66.0)	58.9 (53.1 to 64.7)	59.4 (53.5 to 65.4)
Week 72 (n = 253,257,251)	61.2 (55.2 to 67.1)	61.0 (55.2 to 66.8)	56.8 (50.7 to 62.9)
Week 76 (n = 247,253,251)	60.1 (54.1 to 66.2)	67.8 (62.3 to 73.3)	64.2 (58.3 to 70.0)
Week 80 (n = 247,259,251)	64.0 (58.1 to 70.0)	61.7 (56.1 to 67.4)	60.5 (54.5 to 66.4)
Week 84 (n = 248,260,252)	61.0 (55.0 to 67.0)	64.4 (58.8 to 70.1)	64.4 (58.6 to 70.2)
Week 88 (n = 245,256,247)	59.6 (53.5 to 65.7)	59.8 (54.0 to 65.7)	62.7 (56.9 to 68.5)
Week 92 (n = 248,258,248)	63.2 (57.3 to 69.1)	63.3 (57.6 to 69.0)	64.6 (58.7 to 70.4)
Week 96 (n = 242,259,245)	60.3 (54.1 to 66.4)	59.7 (53.9 to 65.5)	62.5 (56.5 to 68.6)
Week 100 (n = 254,258,247)	63.0 (57.3 to 68.8)	60.5 (54.8 to 66.2)	66.0 (60.1 to 71.8)

No statistical analyses for this end point

Secondary: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 310,308,306)	53.6 (48.1 to 59.1)	62.6 (57.3 to 67.9)	61.1 (55.7 to 66.5)
Week 8 (n = 309,308,304)	64.7 (59.4 to 70.0)	71.1 (66.1 to 76.0)	67.6 (62.4 to 72.8)
Week 12 (n = 305,303,302)	71.9 (66.9 to 76.9)	74.3 (69.4 to 79.2)	75.4 (70.6 to 80.3)
Week 16 (n = 296,296,299)	74.9 (70.0 to 79.9)	81.4 (77.0 to 85.8)	77.5 (72.7 to 82.2)
Week 20 (n = 294,292,296)	78.2 (73.6 to 82.9)	78.4 (73.7 to 83.1)	76.4 (71.6 to 81.1)
Week 24 (n = 292,293,294)	80.5 (76.0 to 85.0)	83.3 (79.0 to 87.5)	71.0 (65.8 to 76.1)
Week 28 (n = 283,287,284)	77.4 (72.5 to 82.2)	81.0 (76.6 to 85.5)	79.1 (74.4 to 83.8)
Week 32 (n = 267,268,275)	79.4 (74.6 to 84.3)	77.1 (72.2 to 82.0)	81.3 (76.8 to 85.8)
Week 36 (n = 268,268,268)	79.2 (74.4 to 84.1)	82.6 (78.2 to 87.1)	78.3 (73.5 to 83.1)
Week 40 (n = 275,269,263)	76.3 (71.3 to 81.3)	84.3 (80.0 to 88.6)	77.1 (72.0 to 82.2)
Week 44 (n = 268,269,266)	80.7 (75.9 to 85.4)	81.9 (77.3 to 86.4)	77.9 (73.0 to 82.7)
Week 48 (n = 264,266,266)	79.2 (74.4 to 84.1)	82.0 (77.5 to 86.6)	79.3 (74.4 to 84.1)
Week 52 (n = 264,267,253)	78.4 (73.5 to 83.4)	78.4 (73.5 to 83.2)	81.2 (76.4 to 85.9)
Week 56 (n = 260,263,256)	83.0 (78.5 to 87.6)	81.3 (76.6 to 86.0)	81.4 (76.7 to 86.1)
Week 60 (n = 270,261,261)	80.4 (75.7 to 85.1)	81.3 (76.7 to 85.9)	81.4 (76.8 to 86.1)
Week 64 (n = 259,263,263)	80.2 (75.4 to 85.1)	80.6 (75.9 to 85.2)	79.7 (74.9 to 84.5)
Week 68 (n = 251,257,253)	79.1 (74.1 to 84.0)	78.9 (74.0 to 83.8)	79.1 (74.2 to 84.0)
Week 72 (n = 253,257,251)	79.7 (74.8 to 84.6)	78.1 (73.2 to 83.0)	80.9 (76.1 to 85.7)
Week 76 (n = 247,253,251)	79.9 (74.9 to 84.8)	78.9 (74.0 to 83.8)	82.9 (78.3 to 87.5)
Week 80 (n = 247,259,251)	81.0 (76.1 to 85.9)	80.3 (75.5 to 85.0)	78.3 (73.2 to 83.4)
Week 84 (n = 248,260,252)	77.1 (71.9 to 82.3)	82.0 (77.5 to 86.5)	82.6 (77.9 to 87.2)
Week 88 (n = 245,256,247)	79.3 (74.2 to 84.3)	80.5 (75.8 to 85.2)	80.5 (75.6 to 85.5)
Week 92 (n = 248,258,248)	81.4 (76.6 to 86.3)	82.1 (77.5 to 86.7)	83.2 (78.6 to 87.7)
Week 96 (n = 242,259,245)	82.6 (77.8 to 87.3)	77.4 (72.5 to 82.4)	81.2 (76.3 to 86.0)
Week 100 (n = 254,258,247)	81.1 (76.3 to 85.9)	77.0 (71.9 to 82.0)	85.2 (80.9 to 89.6)

No statistical analyses for this end point

Secondary: Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 310,308,306)	86.1 (82.3 to 90.0)	90.8 (87.7 to 94.0)	88.9 (85.4 to 92.3)
Week 8 (n = 309,308,304)	89.7 (86.4 to 93.0)	91.9 (88.8 to 94.9)	91.1 (87.9 to 94.2)
Week 12 (n = 305,303,302)	92.5 (89.6 to 95.4)	94.7 (92.2 to 97.2)	92.7 (89.8 to 95.6)
Week 16 (n = 296,296,299)	91.2 (88.0 to 94.4)	94.9 (92.4 to 97.4)	93.7 (90.9 to 96.4)
Week 20 (n = 294,292,296)	93.9 (91.2 to 96.6)	93.1 (90.2 to 96.0)	92.2 (89.2 to 95.2)
Week 24 (n = 292,293,294)	93.1 (90.2 to 96.0)	93.8 (91.0 to 96.5)	89.9 (86.5 to 93.3)
Week 28 (n = 283,287,284)	90.4 (87.0 to 93.8)	94.1 (91.4 to 96.8)	91.5 (88.3 to 94.6)
Week 32 (n = 267,268,275)	92.1 (88.9 to 95.3)	95.1 (92.6 to 97.7)	91.3 (88.0 to 94.6)
Week 36 (n = 268,268,268)	92.1 (88.9 to 95.3)	93.2 (90.2 to 96.2)	90.4 (87.0 to 93.9)
Week 40 (n = 275,269,263)	90.9 (87.5 to 94.3)	94.0 (91.1 to 96.8)	93.2 (90.2 to 96.2)
Week 44 (n = 268,269,266)	91.0 (87.6 to 94.4)	94.5 (91.8 to 97.2)	91.0 (87.6 to 94.4)
Week 48 (n = 264,266,266)	95.2 (92.6 to 97.7)	93.7 (90.8 to 96.5)	91.3 (88.0 to 94.6)
Week 52 (n = 264,267,253)	89.8 (86.1 to 93.4)	91.3 (88.0 to 94.7)	91.0 (87.5 to 94.5)
Week 56 (n = 260,263,256)	91.4 (88.0 to 94.8)	93.9 (91.0 to 96.7)	90.6 (87.1 to 94.2)
Week 60 (n = 270,261,261)	89.5 (85.9 to 93.2)	93.5 (90.5 to 96.4)	92.8 (89.7 to 95.9)
Week 64 (n = 259,263,263)	91.3 (87.9 to 94.7)	92.7 (89.6 to 95.8)	92.0 (88.7 to 95.2)
Week 68 (n = 251,257,253)	92.1 (88.8 to 95.4)	92.9 (89.8 to 96.0)	91.9 (88.6 to 95.2)
Week 72 (n = 253,257,251)	88.5 (84.6 to 92.5)	91.9 (88.7 to 95.2)	90.0 (86.3 to 93.7)
Week 76 (n = 247,253,251)	87.8 (83.8 to 91.9)	91.2 (87.8 to 94.7)	92.5 (89.4 to 95.7)
Week 80 (n = 247,259,251)	89.2 (85.4 to 93.0)	91.5 (88.1 to 94.9)	89.6 (85.9 to 93.4)
Week 84 (n = 248,260,252)	87.1 (82.9 to 91.2)	92.4 (89.2 to 95.6)	93.5 (90.5 to 96.5)
Week 88 (n = 245,256,247)	87.3 (83.2 to 91.4)	90.3 (86.7 to 93.8)	89.9 (86.1 to 93.7)
Week 92 (n = 248,258,248)	89.4 (85.5 to 93.2)	91.1 (87.6 to 94.6)	90.8 (87.3 to 94.3)
Week 96 (n = 242,259,245)	90.7 (87.0 to 94.4)	88.9 (85.1 to 92.6)	90.5 (86.8 to 94.2)
Week 100 (n = 254,258,247)	88.3 (84.3 to 92.3)	86.8 (82.7 to 90.9)	92.0 (88.7 to 95.4)

No statistical analyses for this end point

Secondary: Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population

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End point title

Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population

End point description

BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, average of Weeks 48, 52, and 56

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	200	215	212
Units: Percentage of participants
number (confidence interval 95%)
Gaining ≥15 Letters	28.6 (22.3 to 34.8)	35.5 (29.3 to 41.7)	33.8 (27.7 to 39.9)
Gaining ≥10 Letters	57.5 (50.7 to 64.4)	59.6 (53.2 to 65.9)	57.5 (50.9 to 64.1)
Gaining ≥5 Letters	80.0 (74.4 to 85.5)	77.2 (71.6 to 82.8)	84.5 (79.6 to 89.3)
Gaining ≥0 Letters	91.5 (87.6 to 95.3)	93.5 (90.2 to 96.8)	91.6 (87.9 to 95.3)

Gaining ≥15 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥15 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-14

upper limit

3.5

Gaining ≥15 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥15 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

427

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7

upper limit

10.3

Gaining ≥10 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥10 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-9.5

upper limit

9.5

Gaining ≥10 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥10 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

427

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

11.3

Gaining ≥5 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥5 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

427

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-7.2

Confidence interval

level

95%

sides

2-sided

lower limit

-14.6

upper limit

0.2

Gaining ≥5 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥5 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-4.5

Confidence interval

level

95%

sides

2-sided

lower limit

-11.9

upper limit

2.9

Gaining ≥0 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥0 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.5

upper limit

5.2

Gaining ≥0 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants gaining ≥0 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

427

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

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End point title

Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 234,241,236)	8.9 (5.3 to 12.5)	14.9 (10.6 to 19.3)	12.7 (8.6 to 16.9)
Week 8 (n = 232,240,234)	14.3 (9.9 to 18.8)	19.2 (14.6 to 23.8)	17.8 (13.1 to 22.6)
Week 12 (n = 230,235,235)	15.7 (11.1 to 20.3)	22.2 (17.2 to 27.1)	24.2 (19.0 to 29.5)
Week 16 (n = 222,229,232)	21.3 (16.0 to 26.6)	28.2 (22.6 to 33.8)	24.0 (18.6 to 29.3)
Week 20 (n = 223,227,229)	26.5 (20.8 to 32.2)	27.7 (22.2 to 33.3)	26.2 (20.7 to 31.6)
Week 24 (n = 219,228,228)	27.1 (21.3 to 32.9)	34.3 (28.4 to 40.2)	27.5 (22.0 to 33.1)
Week 28 (n = 212,224,217)	21.5 (16.0 to 27.0)	30.7 (25.0 to 36.4)	32.8 (26.8 to 38.7)
Week 32 (n = 195,205,209)	27.2 (21.0 to 33.5)	37.5 (31.2 to 43.8)	29.5 (23.6 to 35.4)
Week 36 (n = 194,205,205)	23.5 (17.6 to 29.5)	41.9 (35.5 to 48.2)	34.9 (28.6 to 41.2)
Week 40 (n = 202,204,200)	27.6 (21.5 to 33.8)	37.7 (31.2 to 44.1)	33.5 (27.0 to 39.9)
Week 44 (n = 199,209,202)	27.2 (21.1 to 33.4)	39.7 (33.3 to 46.0)	37.0 (30.6 to 43.4)
Week 48 (n = 195,210,203)	32.5 (26.0 to 39.1)	39.6 (33.1 to 46.0)	36.3 (30.1 to 42.5)
Week 52 (n = 197,209,196)	30.7 (24.3 to 37.1)	35.9 (29.6 to 42.1)	37.4 (30.9 to 43.9)
Week 56 (n = 194,207,198)	37.7 (31.0 to 44.5)	38.8 (32.3 to 45.2)	34.3 (27.9 to 40.8)
Week 60 (n = 200,198,199)	33.1 (26.6 to 39.6)	42.2 (35.6 to 48.9)	38.9 (32.4 to 45.5)
Week 64 (n = 191,202,200)	37.9 (31.1 to 44.7)	43.5 (37.0 to 50.0)	36.0 (29.5 to 42.6)
Week 68 (n = 187,197,193)	37.4 (30.7 to 44.2)	45.4 (38.7 to 52.1)	39.0 (32.4 to 45.5)
Week 72 (n = 186,196,189)	35.6 (28.8 to 42.4)	39.6 (33.1 to 46.0)	36.6 (29.8 to 43.3)
Week 76 (n = 180,195,189)	37.6 (30.6 to 44.6)	45.3 (38.8 to 51.8)	37.2 (30.5 to 43.9)
Week 80 (n = 177,203,190)	39.7 (32.7 to 46.8)	43.2 (36.8 to 49.7)	40.5 (33.6 to 47.3)
Week 84 (n = 181,203,192)	40.7 (33.7 to 47.8)	43.2 (36.8 to 49.7)	41.2 (34.3 to 48.1)
Week 88 (n = 179,196,185)	39.1 (32.1 to 46.2)	40.7 (34.4 to 47.1)	38.0 (31.2 to 44.8)
Week 92 (n = 180,199,188)	40.2 (33.2 to 47.3)	42.1 (35.7 to 48.5)	40.4 (33.6 to 47.3)
Week 96 (n = 174,201,187)	42.9 (35.6 to 50.2)	41.2 (34.9 to 47.6)	40.1 (33.2 to 47.0)
Week 100 (n = 185,199,186)	41.7 (34.6 to 48.7)	42.5 (36.1 to 48.9)	41.2 (34.3 to 48.1)

No statistical analyses for this end point

Secondary: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

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End point title

Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 234,241,236)	25.2 (19.7 to 30.7)	32.0 (26.3 to 37.7)	29.2 (23.5 to 35.0)
Week 8 (n = 232,240,234)	31.1 (25.2 to 37.1)	37.2 (31.3 to 43.1)	43.9 (37.7 to 50.2)
Week 12 (n = 230,235,235)	36.9 (30.8 to 43.1)	46.5 (40.3 to 52.6)	48.9 (42.6 to 55.2)
Week 16 (n = 222,229,232)	43.8 (37.3 to 50.3)	47.8 (41.4 to 54.1)	49.8 (43.5 to 56.2)
Week 20 (n = 223,227,229)	44.9 (38.4 to 51.4)	53.7 (47.5 to 59.9)	51.5 (45.1 to 57.9)
Week 24 (n = 219,228,228)	57.6 (51.1 to 64.1)	57.9 (51.7 to 64.2)	49.9 (43.5 to 56.3)
Week 28 (n = 212,224,217)	55.3 (48.6 to 61.9)	56.6 (50.3 to 62.9)	57.4 (50.8 to 63.9)
Week 32 (n = 195,205,209)	59.0 (52.2 to 65.9)	59.6 (53.1 to 66.0)	53.1 (46.5 to 59.7)
Week 36 (n = 194,205,205)	59.0 (52.1 to 65.9)	66.3 (60.0 to 72.5)	55.8 (49.1 to 62.5)
Week 40 (n = 202,204,200)	55.5 (48.7 to 62.4)	59.7 (53.1 to 66.4)	54.5 (47.7 to 61.4)
Week 44 (n = 199,209,202)	55.0 (48.1 to 61.9)	59.2 (52.7 to 65.7)	58.1 (51.3 to 64.8)
Week 48 (n = 195,210,203)	57.1 (50.2 to 64.0)	58.5 (52.0 to 65.0)	62.6 (56.0 to 69.2)
Week 52 (n = 197,209,196)	60.0 (53.1 to 66.8)	58.8 (52.2 to 65.3)	61.0 (54.2 to 67.8)
Week 56 (n = 194,207,198)	65.0 (58.3 to 71.7)	62.9 (56.5 to 69.3)	60.1 (53.4 to 66.8)
Week 60 (n = 200,198,199)	61.5 (54.7 to 68.2)	63.4 (56.9 to 69.9)	61.3 (54.5 to 68.0)
Week 64 (n = 191,202,200)	67.7 (61.1 to 74.3)	59.8 (53.3 to 66.2)	59.7 (53.0 to 66.4)
Week 68 (n = 187,197,193)	64.1 (57.4 to 70.8)	60.7 (54.2 to 67.2)	60.6 (53.9 to 67.3)
Week 72 (n = 186,196,189)	62.6 (55.8 to 69.5)	62.5 (56.0 to 69.0)	56.7 (49.8 to 63.7)
Week 76 (n = 180,195,189)	61.8 (54.8 to 68.9)	66.8 (60.5 to 73.0)	66.2 (59.6 to 72.9)
Week 80 (n = 177,203,190)	66.7 (59.8 to 73.5)	62.4 (56.0 to 68.8)	62.8 (56.0 to 69.6)
Week 84 (n = 181,203,192)	63.2 (56.3 to 70.1)	65.3 (59.0 to 71.6)	67.1 (60.5 to 73.6)
Week 88 (n = 179,196,185)	60.2 (53.2 to 67.3)	60.9 (54.3 to 67.6)	61.9 (55.1 to 68.7)
Week 92 (n = 180,199,188)	63.2 (56.2 to 70.2)	65.1 (58.7 to 71.5)	65.0 (58.2 to 71.7)
Week 96 (n = 174,201,187)	58.8 (51.5 to 66.0)	60.6 (54.0 to 67.1)	63.8 (59.6 to 70.6)
Week 100 (n = 185,199,186)	64.0 (57.3 to 70.7)	62.4 (56.0 to 68.8)	64.8 (58.0 to 71.6)

No statistical analyses for this end point

Secondary: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

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End point title

Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 234,241,236)	53.8 (47.5 to 60.2)	63.1 (57.1 to 69.1)	62.8 (56.7 to 68.9)
Week 8 (n = 232,240,234)	63.4 (57.2 to 69.6)	70.5 (64.8 to 76.2)	70.4 (64.6 to 76.2)
Week 12 (n = 230,235,235)	72.7 (66.9 to 78.4)	75.4 (69.9 to 80.8)	77.0 (71.6 to 82.4)
Week 16 (n = 222,229,232)	75.6 (70.0 to 81.3)	81.3 (76.3 to 86.3)	79.3 (74.1 to 84.5)
Week 20 (n = 223,227,229)	79.0 (73.6 to 84.3)	79.3 (74.0 to 84.6)	78.2 (72.9 to 83.5)
Week 24 (n = 219,228,228)	81.7 (76.6 to 86.8)	82.9 (78.1 to 87.7)	71.4 (65.5 to 77.2)
Week 28 (n = 212,224,217)	76.9 (71.2 to 82.5)	81.7 (76.6 to 86.7)	80.0 (74.8 to 85.3)
Week 32 (n = 195,205,209)	80.0 (74.4 to 85.6)	77.6 (72.0 to 83.1)	83.7 (78.8 to 88.7)
Week 36 (n = 194,205,205)	80.5 (74.9 to 86.1)	82.9 (77.9 to 88.0)	79.6 (74.1 to 85.1)
Week 40 (n = 202,204,200)	77.1 (71.3 to 82.8)	85.3 (80.5 to 90.1)	80.0 (74.5 to 85.6)
Week 44 (n = 199,209,202)	81.4 (76.0 to 86.8)	82.5 (77.4 to 87.6)	80.8 (75.4 to 86.2)
Week 48 (n = 195,210,203)	79.5 (73.8 to 85.2)	80.0 (74.6 to 85.4)	80.8 (75.4 to 86.2)
Week 52 (n = 197,209,196)	78.7 (72.9 to 84.4)	75.3 (69.5 to 81.1)	82.3 (77.1 to 87.6)
Week 56 (n = 194,207,198)	84.0 (78.9 to 89.2)	81.2 (75.9 to 86.4)	81.9 (76.6 to 87.1)
Week 60 (n = 200,198,199)	81.0 (75.5 to 86.4)	80.5 (75.2 to 85.8)	80.0 (74.5 to 85.5)
Week 64 (n = 191,202,200)	80.7 (75.1 to 86.3)	80.2 (74.9 to 85.6)	80.3 (74.8 to 85.7)
Week 68 (n = 187,197,193)	82.0 (76.5 to 87.5)	78.3 (72.6 to 83.9)	79.7 (74.1 to 85.2)
Week 72 (n = 186,196,189)	81.5 (76.0 to 87.0)	77.3 (71.6 to 82.9)	80.9 (75.4 to 86.5)
Week 76 (n = 180,195,189)	79.5 (73.7 to 85.4)	78.0 (72.4 to 83.6)	83.8 (78.6 to 88.9)
Week 80 (n = 177,203,190)	82.0 (76.3 to 87.7)	80.5 (75.2 to 85.8)	80.0 (74.3 to 85.7)
Week 84 (n = 181,203,192)	78.6 (72.6 to 84.6)	83.0 (78.0 to 87.9)	81.8 (76.4 to 87.3)
Week 88 (n = 179,196,185)	77.9 (71.8 to 83.9)	80.7 (75.4 to 86.1)	80.6 (74.9 to 86.2)
Week 92 (n = 180,199,188)	80.5 (74.8 to 86.3)	82.1 (76.8 to 87.3)	82.5 (77.2 to 87.9)
Week 96 (n = 174,201,187)	82.7 (77.1 to 88.3)	76.9 (71.2 to 82.5)	82.4 (76.9 to 87.8)
Week 100 (n = 185,199,186)	80.0 (74.3 to 85.8)	78.2 (72.6 to 83.9)	85.7 (80.8 to 90.7)

No statistical analyses for this end point

Secondary: Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

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End point title

Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 234,241,236)	86.3 (81.9 to 90.7)	90.9 (87.3 to 94.5)	90.2 (86.5 to 94.0)
Week 8 (n = 232,240,234)	91.4 (87.8 to 95.0)	93.3 (90.2 to 96.5)	93.1 (89.9 to 96.4)
Week 12 (n = 230,235,235)	93.5 (90.4 to 96.6)	96.2 (93.7 to 98.6)	92.8 (89.4 to 96.1)
Week 16 (n = 222,229,232)	91.5 (87.8 to 95.1)	94.7 (91.9 to 97.6)	94.5 (91.6 to 97.4)
Week 20 (n = 223,227,229)	94.2 (91.2 to 97.2)	92.5 (89.1 to 95.9)	92.1 (88.6 to 95.6)
Week 24 (n = 219,228,228)	94.0 (90.9 to 97.1)	93.4 (90.2 to 96.6)	89.0 (85.0 to 93.1)
Week 28 (n = 212,224,217)	90.9 (87.0 to 94.8)	94.2 (91.1 to 97.2)	92.6 (89.1 to 96.1)
Week 32 (n = 195,205,209)	92.3 (88.5 to 96.0)	94.2 (91.0 to 97.3)	91.4 (87.7 to 95.2)
Week 36 (n = 194,205,205)	93.1 (89.5 to 96.7)	93.7 (90.4 to 97.0)	89.4 (85.2 to 93.6)
Week 40 (n = 202,204,200)	91.0 (87.0 to 94.9)	93.6 (90.3 to 97.0)	92.5 (88.9 to 96.2)
Week 44 (n = 199,209,202)	91.8 (88.0 to 95.6)	93.4 (90.0 to 96.7)	91.6 (87.8 to 95.4)
Week 48 (n = 195,210,203)	95.5 (92.6 to 98.4)	91.9 (88.2 to 95.6)	93.1 (89.7 to 96.6)
Week 52 (n = 197,209,196)	89.8 (85.6 to 94.0)	89.5 (85.4 to 93.6)	90.9 (87.0 to 94.9)
Week 56 (n = 194,207,198)	91.7 (87.8 to 95.6)	92.7 (89.2 to 96.3)	90.9 (86.9 to 94.9)
Week 60 (n = 200,198,199)	89.9 (85.7 to 94.1)	93.5 (90.1 to 96.9)	91.9 (88.2 to 95.7)
Week 64 (n = 191,202,200)	92.0 (88.1 to 95.9)	92.6 (89.1 to 96.1)	92.4 (88.7 to 96.1)
Week 68 (n = 187,197,193)	92.0 (88.1 to 95.8)	93.4 (90.0 to 96.8)	91.8 (88.0 to 95.6)
Week 72 (n = 186,196,189)	88.7 (84.1 to 93.2)	92.0 (88.4 to 95.6)	89.3 (84.9 to 93.7)
Week 76 (n = 180,195,189)	86.8 (81.8 to 91.7)	90.8 (86.8 to 94.8)	91.6 (87.8 to 95.5)
Week 80 (n = 177,203,190)	89.5 (85.0 to 94.0)	90.7 (86.7 to 94.7)	90.1 (85.8 to 94.3)
Week 84 (n = 181,203,192)	87.4 (82.6 to 92.3)	92.2 (88.5 to 95.8)	92.5 (88.9 to 96.1)
Week 88 (n = 179,196,185)	85.6 (80.4 to 90.7)	88.8 (84.5 to 93.2)	89.2 (84.7 to 93.7)
Week 92 (n = 180,199,188)	88.8 (84.2 to 93.4)	90.5 (86.5 to 94.6)	91.0 (86.9 to 95.1)
Week 96 (n = 174,201,187)	90.1 (85.7 to 94.6)	87.2 (82.6 to 91.7)	90.3 (86.1 to 94.6)
Week 100 (n = 185,199,186)	87.8 (83.1 to 92.6)	86.1 (81.4 to 90.8)	92.0 (88.1 to 95.9)

No statistical analyses for this end point

Secondary: Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population

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End point title

Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, average of Weeks 48, 52, and 56

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	271	276	276
Units: Percentage of participants
number (confidence interval 95%)
Avoiding a Loss of ≥15 Letters	98.1 (96.5 to 99.7)	98.6 (97.2 to 100.0)	98.9 (97.6 to 100.0)
Avoiding a Loss of ≥10 Letters	96.3 (94.1 to 98.5)	98.2 (96.6 to 99.8)	98.1 (96.5 to 99.7)
Avoiding a Loss of ≥5 Letters	95.2 (92.7 to 97.7)	96.7 (94.7 to 98.8)	96.3 (94.1 to 98.5)

Avoiding a Loss of ≥15 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants avoiding a loss of ≥15 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

547

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

1.3

Avoiding a Loss of ≥15 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants avoiding a loss of ≥15 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

1.5

Avoiding a Loss of ≥10 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants avoiding a loss of ≥10 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

547

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.6

upper limit

0.9

Avoiding a Loss of ≥10 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants avoiding a loss of ≥10 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

2.2

Avoiding a Loss of ≥5 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants avoiding a loss of ≥5 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

547

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

2.2

Avoiding a Loss of ≥5 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants avoiding a loss of ≥5 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

3.4

Secondary: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 310,308,306)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)
Week 8 (n = 309,308,304)	99.7 (99.0 to 100.0)	100.0 (100.0 to 100.0)	99.3 (98.4 to 100.0)
Week 12 (n = 305,303,302)	99.3 (98.5 to 100.0)	100.0 (100.0 to 100.0)	99.7 (99.0 to 100.0)
Week 16 (n = 296,296,299)	99.7 (99.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)
Week 20 (n = 294,292,296)	99.3 (98.4 to 100.0)	99.3 (98.4 to 100.0)	99.6 (99.0 to 100.0)
Week 24 (n = 292,293,294)	99.6 (98.9 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)
Week 28 (n = 283,287,284)	99.3 (98.2 to 100.0)	99.7 (99.0 to 100.0)	99.6 (99.0 to 100.0)
Week 32 (n = 267,268,275)	99.6 (98.8 to 100.0)	100.0 (100.0 to 100.0)	99.3 (98.3 to 100.0)
Week 36 (n = 268,268,268)	99.2 (98.0 to 100.0)	99.2 (98.2 to 100.0)	99.6 (98.8 to 100.0)
Week 40 (n = 275,269,263)	98.8 (97.5 to 100.0)	99.3 (98.2 to 100.0)	99.6 (98.8 to 100.0)
Week 44 (n = 268,269,266)	98.8 (97.5 to 100.0)	98.9 (97.7 to 100.0)	100.0 (100.0 to 100.0)
Week 48 (n = 264,266,266)	98.4 (96.9 to 100.0)	98.1 (96.5 to 99.7)	99.3 (98.3 to 100.0)
Week 52 (n = 264,267,253)	97.2 (95.2 to 99.2)	98.1 (96.5 to 99.7)	98.4 (96.8 to 99.9)
Week 56 (n = 260,263,256)	98.4 (96.9 to 99.9)	98.5 (97.0 to 100.0)	98.4 (96.9 to 99.9)
Week 60 (n = 270,261,261)	98.1 (96.4 to 99.7)	98.5 (97.0 to 99.9)	99.2 (98.1 to 100.0)
Week 64 (n = 259,263,263)	98.8 (97.4 to 100.0)	97.7 (95.8 to 99.5)	98.8 (97.5 to 100.0)
Week 68 (n = 251,257,253)	99.1 (98.0 to 100.0)	98.0 (96.3 to 99.7)	98.8 (97.5 to 100.0)
Week 72 (n = 253,257,251)	97.2 (95.1 to 99.2)	98.8 (97.5 to 100.0)	98.8 (97.5 to 100.0)
Week 76 (n = 247,253,251)	96.6 (94.4 to 98.9)	98.0 (96.3 to 99.7)	98.0 (96.3 to 99.7)
Week 80 (n = 247,259,251)	97.6 (95.7 to 99.5)	96.9 (94.8 to 99.0)	99.1 (98.0 to 100.0)
Week 84 (n = 248,260,252)	97.1 (95.0 to 99.2)	98.1 (96.5 to 99.7)	99.1 (98.0 to 100.0)
Week 88 (n = 245,256,247)	97.1 (95.0 to 99.2)	97.2 (95.2 to 99.2)	97.9 (96.1 to 99.7)
Week 92 (n = 248,258,248)	97.1 (95.0 to 99.2)	97.4 (95.5 to 99.3)	98.3 (96.6 to 99.9)
Week 96 (n = 242,259,245)	97.4 (95.3 to 99.4)	96.6 (94.4 to 98.8)	97.8 (95.9 to 99.7)
Week 100 (n = 254,258,247)	96.3 (93.9 to 98.7)	97.0 (94.9 to 99.0)	98.4 (96.8 to 99.9)

No statistical analyses for this end point

Secondary: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 310,308,306)	98.7 (97.5 to 99.9)	100.0 (100.0 to 100.0)	99.4 (98.5 to 100.0)
Week 8 (n = 309,308,304)	98.4 (97.0 to 99.8)	100.0 (100.0 to 100.0)	99.0 (97.9 to 100.0)
Week 12 (n = 305,303,302)	98.7 (97.4 to 100.0)	100.0 (100.0 to 100.0)	99.3 (98.4 to 100.0)
Week 16 (n = 296,296,299)	99.3 (98.4 to 100.0)	99.3 (98.4 to 100.0)	99.7 (99.0 to 100.0)
Week 20 (n = 294,292,296)	99.0 (97.8 to 100.0)	98.6 (97.3 to 100.0)	99.3 (98.4 to 100.0)
Week 24 (n = 292,293,294)	98.6 (97.2 to 100.0)	99.7 (99.0 to 100.0)	99.3 (98.4 to 100.0)
Week 28 (n = 283,287,284)	97.4 (95.6 to 99.3)	99.0 (97.8 to 100.0)	98.6 (97.2 to 100.0)
Week 32 (n = 267,268,275)	99.2 (98.1 to 100.0)	98.5 (97.0 to 99.9)	98.5 (97.1 to 99.9)
Week 36 (n = 268,268,268)	98.4 (96.9 to 99.9)	98.9 (97.6 to 100.0)	99.2 (98.2 to 100.0)
Week 40 (n = 275,269,263)	97.7 (95.9 to 99.5)	99.3 (98.2 to 100.0)	98.5 (97.0 to 99.9)
Week 44 (n = 268,269,266)	97.3 (95.4 to 99.3)	98.2 (96.6 to 99.8)	99.2 (98.2 to 100.0)
Week 48 (n = 264,266,266)	98.1 (96.4 to 99.7)	97.8 (96.0 to 99.5)	98.5 (97.1 to 99.9)
Week 52 (n = 264,267,253)	95.3 (92.8 to 97.9)	97.0 (95.0 to 99.0)	96.8 (94.6 to 99.0)
Week 56 (n = 260,263,256)	97.2 (95.2 to 99.2)	98.1 (96.5 to 99.7)	96.5 (94.3 to 98.7)
Week 60 (n = 270,261,261)	96.9 (94.8 to 99.0)	97.3 (95.4 to 99.3)	98.1 (96.4 to 99.7)
Week 64 (n = 259,263,263)	98.0 (96.3 to 99.7)	96.5 (94.2 to 98.7)	98.1 (96.4 to 99.7)
Week 68 (n = 251,257,253)	96.9 (94.7 to 99.0)	97.6 (95.8 to 99.5)	98.4 (96.9 to 100.0)
Week 72 (n = 253,257,251)	96.0 (93.6 to 98.4)	98.0 (96.4 to 99.7)	97.6 (95.7 to 99.5)
Week 76 (n = 247,253,251)	95.9 (93.4 to 98.4)	95.6 (93.1 to 98.1)	97.6 (95.7 to 99.5)
Week 80 (n = 247,259,251)	96.3 (94.0 to 98.7)	96.2 (93.8 to 98.5)	97.6 (95.9 to 99.5)
Week 84 (n = 248,260,252)	95.5 (93.0 to 98.1)	97.0 (95.0 to 99.0)	99.1 (98.0 to 100.0)
Week 88 (n = 245,256,247)	95.0 (92.3 to 97.7)	95.6 (93.1 to 98.1)	96.7 (94.5 to 98.9)
Week 92 (n = 248,258,248)	95.9 (93.3 to 98.4)	96.5 (94.3 to 98.7)	97.5 (95.5 to 99.5)
Week 96 (n = 242,259,245)	96.9 (94.7 to 99.2)	94.3 (91.5 to 97.1)	96.6 (94.3 to 98.9)
Week 100 (n = 254,258,247)	94.3 (91.5 to 97.2)	94.6 (91.8 to 97.3)	97.1 (95.1 to 99.2)

No statistical analyses for this end point

Secondary: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Top of page

End point title

Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 310,308,306)	97.7 (96.1 to 99.4)	97.4 (95.6 to 99.1)	96.4 (94.4 to 98.4)
Week 8 (n = 309,308,304)	96.4 (94.4 to 98.5)	98.7 (97.5 to 100.0)	97.3 (95.5 to 99.1)
Week 12 (n = 305,303,302)	98.0 (96.5 to 99.6)	98.0 (96.4 to 99.6)	98.4 (97.0 to 99.8)
Week 16 (n = 296,296,299)	97.3 (95.5 to 99.1)	98.6 (97.3 to 100.0)	98.7 (97.4 to 100.0)
Week 20 (n = 294,292,296)	96.9 (95.0 to 98.9)	97.2 (95.4 to 99.1)	97.3 (95.4 to 99.1)
Week 24 (n = 292,293,294)	96.9 (94.9 to 98.9)	96.9 (94.9 to 98.9)	96.6 (94.6 to 98.7)
Week 28 (n = 283,287,284)	96.4 (94.2 to 98.6)	97.6 (95.8 to 99.3)	96.1 (93.9 to 98.4)
Week 32 (n = 267,268,275)	96.6 (94.4 to 98.8)	97.4 (95.5 to 99.3)	97.5 (95.6 to 99.3)
Week 36 (n = 268,268,268)	96.2 (93.9 to 98.5)	97.3 (95.4 to 99.3)	97.7 (96.0 to 99.5)
Week 40 (n = 275,269,263)	95.2 (92.6 to 97.7)	95.8 (93.4 to 98.2)	97.7 (95.9 to 99.5)
Week 44 (n = 268,269,266)	95.2 (92.6 to 97.7)	96.7 (94.6 to 98.8)	95.8 (93.4 to 98.2)
Week 48 (n = 264,266,266)	96.6 (94.4 to 98.8)	96.7 (94.5 to 98.8)	96.9 (94.9 to 99.0)
Week 52 (n = 264,267,253)	94.2 (91.4 to 97.0)	95.9 (93.5 to 98.3)	94.9 (92.2 to 97.6)
Week 56 (n = 260,263,256)	96.0 (93.7 to 98.4)	96.2 (93.8 to 98.5)	95.0 (92.4 to 97.6)
Week 60 (n = 270,261,261)	94.0 (91.2 to 96.8)	96.2 (93.8 to 98.5)	97.0 (94.9 to 99.0)
Week 64 (n = 259,263,263)	95.7 (93.2 to 98.2)	96.1 (93.8 to 98.5)	96.1 (93.8 to 98.4)
Week 68 (n = 251,257,253)	94.8 (92.1 to 97.6)	96.4 (94.1 to 98.7)	96.1 (93.8 to 98.5)
Week 72 (n = 253,257,251)	93.3 (90.3 to 96.4)	95.3 (92.7 to 97.9)	94.4 (91.5 to 97.2)
Week 76 (n = 247,253,251)	92.6 (89.4 to 95.9)	94.8 (92.0 to 97.5)	95.2 (92.6 to 97.8)
Week 80 (n = 247,259,251)	94.0 (91.0 to 96.9)	93.4 (90.4 to 96.4)	94.0 (91.1 to 96.9)
Week 84 (n = 248,260,252)	92.8 (89.6 to 96.0)	95.8 (93.4 to 98.2)	97.2 (95.1 to 99.2)
Week 88 (n = 245,256,247)	89.8 (86.0 to 93.5)	92.6 (89.4 to 95.8)	94.7 (91.9 to 97.5)
Week 92 (n = 248,258,248)	93.8 (90.8 to 96.8)	92.7 (89.5 to 95.8)	96.7 (94.4 to 98.9)
Week 96 (n = 242,259,245)	94.9 (92.0 to 97.7)	92.3 (89.1 to 95.5)	95.0 (92.3 to 97.8)
Week 100 (n = 254,258,247)	91.1 (87.6 to 94.6)	88.9 (85.1 to 92.6)	96.4 (94.1 to 98.6)

No statistical analyses for this end point

Secondary: Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population

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End point title

Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, average of Weeks 48, 52, and 56

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	200	215	212
Units: Percentage of participants
number (confidence interval 95%)
Avoiding a Loss of ≥15 Letters	97.9 (96.0 to 99.9)	98.1 (96.3 to 99.9)	99.0 (97.7 to 100.0)
Avoiding a Loss of ≥10 Letters	96.5 (93.9 to 99.0)	97.7 (95.7 to 99.7)	98.6 (97.0 to 100.0)
Avoiding a Loss of ≥5 Letters	95.0 (91.9 to 98.0)	95.8 (93.1 to 98.5)	96.2 (93.6 to 98.8)

Avoiding a Loss of ≥15 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants avoiding a loss of ≥15 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

1.3

Avoiding a Loss of ≥15 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants avoiding a loss of ≥15 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

427

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

1.3

Avoiding a Loss of ≥10 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants avoiding a loss of ≥10 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

0.9

Avoiding a Loss of ≥10 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants avoiding a loss of ≥10 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

427

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

1.6

Avoiding a Loss of ≥5 Letters: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants avoiding a loss of ≥5 letters in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

2.8

Avoiding a Loss of ≥5 Letters: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants avoiding a loss of ≥5 letters in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

427

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.1

upper limit

3.3

Secondary: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Top of page

End point title

Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 234,241,236)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)
Week 8 (n = 232,240,234)	99.6 (98.7 to 100.0)	100.0 (100.0 to 100.0)	99.6 (98.8 to 100.0)
Week 12 (n = 230,235,235)	99.6 (98.7 to 100.0)	100.0 (100.0 to 100.0)	99.6 (98.7 to 100.0)
Week 16 (n = 222,229,232)	99.6 (98.7 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)
Week 20 (n = 223,227,229)	99.1 (97.9 to 100.0)	99.1 (97.9 to 100.0)	100.0 (100.0 to 100.0)
Week 24 (n = 219,228,228)	99.5 (98.6 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)
Week 28 (n = 212,224,217)	99.0 (97.6 to 100.0)	99.6 (98.7 to 100.0)	99.5 (98.6 to 100.0)
Week 32 (n = 195,205,209)	99.5 (98.4 to 100.0)	100.0 (100.0 to 100.0)	99.0 (97.7 to 100.0)
Week 36 (n = 194,205,205)	98.9 (97.3 to 100.0)	99.0 (97.6 to 100.0)	99.5 (98.4 to 100.0)
Week 40 (n = 202,204,200)	98.4 (96.6 to 100.0)	99.0 (97.7 to 100.0)	99.5 (98.4 to 100.0)
Week 44 (n = 199,209,202)	98.9 (97.5 to 100.0)	98.6 (97.0 to 100.0)	100.0 (100.0 to 100.0)
Week 48 (n = 195,210,203)	98.4 (96.6 to 100.0)	97.6 (95.5 to 99.7)	99.0 (97.7 to 100.0)
Week 52 (n = 197,209,196)	96.8 (94.3 to 99.3)	97.6 (95.5 to 99.7)	98.4 (96.6 to 100.0)
Week 56 (n = 194,207,198)	98.4 (96.7 to 100.0)	98.1 (96.2 to 99.9)	98.5 (96.7 to 100.0)
Week 60 (n = 200,198,199)	97.4 (95.2 to 99.6)	98.0 (96.1 to 99.9)	99.0 (97.5 to 100.0)
Week 64 (n = 191,202,200)	98.4 (96.5 to 100.0)	97.0 (94.6 to 99.4)	98.4 (96.7 to 100.0)
Week 68 (n = 187,197,193)	98.9 (97.3 to 100.0)	97.4 (95.2 to 99.6)	98.4 (96.7 to 100.0)
Week 72 (n = 186,196,189)	96.2 (93.4 to 98.9)	98.5 (96.8 to 100.0)	98.4 (96.6 to 100.0)
Week 76 (n = 180,195,189)	95.5 (92.4 to 98.5)	97.4 (95.2 to 99.6)	97.9 (95.9 to 99.9)
Week 80 (n = 177,203,190)	96.7 (94.1 to 99.3)	96.6 (94.1 to 99.1)	98.8 (97.3 to 100.0)
Week 84 (n = 181,203,192)	96.1 (93.2 to 98.9)	98.0 (96.1 to 99.9)	99.5 (98.4 to 100.0)
Week 88 (n = 179,196,185)	96.1 (93.2 to 98.9)	97.5 (95.3 to 99.6)	97.7 (95.5 to 99.9)
Week 92 (n = 180,199,188)	96.1 (93.2 to 98.9)	97.0 (94.7 to 99.3)	98.3 (96.4 to 100.0)
Week 96 (n = 174,201,187)	97.1 (94.6 to 99.6)	96.1 (93.4 to 98.7)	98.9 (97.3 to 100.0)
Week 100 (n = 185,199,186)	96.1 (93.3 to 98.9)	97.1 (94.8 to 99.4)	98.4 (96.6 to 100.0)

No statistical analyses for this end point

Secondary: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

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End point title

Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 234,241,236)	99.6 (98.7 to 100.0)	100.0 (100.0 to 100.0)	99.2 (98.0 to 100.0)
Week 8 (n = 232,240,234)	98.3 (96.6 to 100.0)	100.0 (100.0 to 100.0)	99.6 (98.8 to 100.0)
Week 12 (n = 230,235,235)	99.1 (97.9 to 100.0)	100.0 (100.0 to 100.0)	99.6 (98.7 to 100.0)
Week 16 (n = 222,229,232)	99.1 (97.9 to 100.0)	99.1 (97.9 to 100.0)	100.0 (100.0 to 100.0)
Week 20 (n = 223,227,229)	99.1 (97.9 to 100.0)	98.3 (96.6 to 99.9)	100.0 (100.0 to 100.0)
Week 24 (n = 219,228,228)	99.1 (97.8 to 100.0)	99.6 (98.7 to 100.0)	99.1 (97.9 to 100.0)
Week 28 (n = 212,224,217)	98.0 (96.1 to 99.9)	98.7 (97.2 to 100.0)	98.6 (97.1 to 100.0)
Week 32 (n = 195,205,209)	99.5 (98.4 to 100.0)	98.0 (96.1 to 99.9)	98.1 (96.2 to 99.9)
Week 36 (n = 194,205,205)	97.9 (95.8 to 99.9)	98.5 (96.8 to 100.0)	99.0 (97.6 to 100.0)
Week 40 (n = 202,204,200)	96.9 (94.5 to 99.3)	99.0 (97.7 to 100.0)	97.9 (95.9 to 99.9)
Week 44 (n = 199,209,202)	97.4 (95.2 to 99.6)	97.6 (95.6 to 99.7)	99.0 (97.6 to 100.0)
Week 48 (n = 195,210,203)	97.9 (95.9 to 99.9)	97.1 (94.9 to 99.4)	98.5 (96.9 to 100.0)
Week 52 (n = 197,209,196)	95.3 (92.3 to 98.3)	96.2 (93.6 to 98.8)	96.8 (94.4 to 99.3)
Week 56 (n = 194,207,198)	97.4 (95.2 to 99.6)	97.6 (95.5 to 99.7)	96.4 (93.9 to 99.0)
Week 60 (n = 200,198,199)	96.4 (93.8 to 99.0)	96.5 (93.9 to 99.0)	97.9 (95.9 to 99.9)
Week 64 (n = 191,202,200)	97.3 (95.0 to 99.6)	96.5 (94.0 to 99.1)	97.4 (95.2 to 99.6)
Week 68 (n = 187,197,193)	96.8 (94.3 to 99.3)	96.9 (94.6 to 99.3)	97.9 (95.9 to 99.9)
Week 72 (n = 186,196,189)	95.1 (92.0 to 98.2)	98.0 (96.1 to 99.9)	97.3 (95.0 to 99.6)
Week 76 (n = 180,195,189)	94.9 (91.7 to 98.2)	94.3 (91.1 to 97.6)	97.4 (95.1 to 99.6)
Week 80 (n = 177,203,190)	95.0 (91.8 to 98.2)	95.6 (92.8 to 98.4)	97.3 (94.9 to 99.6)
Week 84 (n = 181,203,192)	94.0 (90.5 to 97.4)	97.1 (94.7 to 99.4)	99.5 (98.4 to 100.0)
Week 88 (n = 179,196,185)	93.9 (90.4 to 97.4)	95.4 (92.5 to 98.3)	96.1 (93.3 to 98.9)
Week 92 (n = 180,199,188)	95.0 (91.8 to 98.2)	96.5 (94.0 to 99.0)	97.2 (94.9 to 99.6)
Week 96 (n = 174,201,187)	96.5 (93.7 to 99.3)	93.6 (90.2 to 97.0)	97.2 (94.8 to 99.6)
Week 100 (n = 185,199,186)	93.9 (90.4 to 97.4)	94.6 (91.5 to 97.7)	97.3 (94.9 to 99.6)

No statistical analyses for this end point

Secondary: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

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End point title

Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 234,241,236)	98.7 (97.3 to 100.0)	97.5 (95.5 to 99.5)	97.0 (94.9 to 99.2)
Week 8 (n = 232,240,234)	96.5 (94.2 to 98.8)	99.2 (98.1 to 100.0)	98.3 (96.6 to 99.9)
Week 12 (n = 230,235,235)	98.3 (96.6 to 99.9)	98.7 (97.3 to 100.0)	98.7 (97.3 to 100.0)
Week 16 (n = 222,229,232)	97.8 (95.8 to 99.7)	98.3 (96.6 to 99.9)	98.7 (97.3 to 100.0)
Week 20 (n = 223,227,229)	97.3 (95.2 to 99.4)	96.5 (94.2 to 98.9)	97.8 (95.9 to 99.7)
Week 24 (n = 219,228,228)	97.7 (95.7 to 99.7)	96.1 (93.5 to 98.6)	96.5 (94.1 to 98.9)
Week 28 (n = 212,224,217)	96.6 (94.1 to 99.0)	97.3 (95.2 to 99.4)	96.8 (94.5 to 99.1)
Week 32 (n = 195,205,209)	97.4 (95.1 to 99.6)	96.6 (94.1 to 99.1)	97.6 (95.5 to 99.1)
Week 36 (n = 194,205,205)	96.3 (93.6 to 99.0)	97.6 (95.4 to 99.7)	98.1 (96.2 to 99.9)
Week 40 (n = 202,204,200)	94.5 (91.3 to 97.6)	95.6 (92.7 to 98.4)	96.9 (94.5 to 99.3)
Week 44 (n = 199,209,202)	95.9 (93.2 to 98.7)	95.8 (93.1 to 98.5)	96.5 (93.9 to 99.0)
Week 48 (n = 195,210,203)	96.4 (93.8 to 99.0)	95.7 (93.0 to 98.5)	97.5 (95.4 to 99.7)
Week 52 (n = 197,209,196)	94.3 (91.1 to 97.6)	94.8 (91.7 to 97.8)	94.4 (91.2 to 97.6)
Week 56 (n = 194,207,198)	95.8 (93.0 to 98.6)	95.6 (92.9 to 98.4)	94.4 (91.3 to 97.6)
Week 60 (n = 200,198,199)	94.4 (91.2 to 97.6)	96.0 (93.3 to 98.7)	96.9 (94.6 to 99.3)
Week 64 (n = 191,202,200)	95.2 (92.2 to 98.3)	96.0 (93.3 to 98.7)	95.8 (93.0 to 98.6)
Week 68 (n = 187,197,193)	94.6 (91.4 to 97.9)	95.9 (93.2 to 98.7)	96.4 (93.8 to 99.0)
Week 72 (n = 186,196,189)	92.6 (88.8 to 96.3)	95.9 (93.2 to 98.7)	94.7 (91.4 to 97.9)
Week 76 (n = 180,195,189)	91.1 (86.9 to 95.3)	93.8 (90.5 to 97.2)	94.7 (91.5 to 97.9)
Week 80 (n = 177,203,190)	92.8 (89.0 to 96.6)	92.6 (89.1 to 96.2)	94.2 (90.9 to 97.5)
Week 84 (n = 181,203,192)	91.9 (87.9 to 95.8)	96.1 (93.4 to 98.7)	96.9 (94.4 to 99.3)
Week 88 (n = 179,196,185)	88.3 (83.6 to 93.0)	91.9 (88.1 to 95.7)	93.5 (89.9 to 97.0)
Week 92 (n = 180,199,188)	92.7 (88.9 to 96.5)	92.5 (88.9 to 96.2)	96.7 (94.1 to 99.3)
Week 96 (n = 174,201,187)	94.8 (91.4 to 98.1)	91.5 (87.7 to 95.4)	95.2 (92.1 to 98.3)
Week 100 (n = 185,199,186)	90.6 (86.4 to 94.9)	88.1 (83.7 to 92.5)	96.8 (94.2 to 99.3)

No statistical analyses for this end point

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

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End point title

Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

End point description

End point type

Secondary

End point timeframe

Baseline, average of Weeks 48, 52, and 56

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	271	276	276	200	215	212
Units: Percentage of participants
number (confidence interval 95%)	32.1 (26.6 to 37.6)	39.1 (33.5 to 44.7)	37.0 (31.5 to 42.5)	31.5 (25.1 to 38.0)	39.2 (32.8 to 45.5)	40.2 (33.7 to 46.6)

ITT: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

547

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-12.6

upper limit

2.9

TN: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-8.6

Confidence interval

level

95%

sides

2-sided

lower limit

-17.8

upper limit

0.5

TN: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

427

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-9.9

upper limit

8.2

ITT: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-5.9

upper limit

9.8

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 310,308,306)	8.7 (5.6 to 11.8)	14.6 (10.8 to 18.4)	13.3 (9.6 to 17.0)
Week 8 (n = 309,308,304)	15.3 (11.3 to 19.3)	20.1 (15.9 to 24.4)	19.9 (15.6 to 24.3)
Week 12 (n = 305,303,302)	17.9 (13.6 to 22.1)	25.7 (21.1 to 30.4)	25.3 (20.6 to 30.0)
Week 16 (n = 296,296,299)	24.1 (19.2 to 28.9)	29.1 (24.2 to 34.0)	25.2 (20.5 to 30.0)
Week 20 (n = 294,292,296)	30.1 (24.9 to 35.2)	30.8 (25.6 to 35.9)	27.7 (22.8 to 32.6)
Week 24 (n = 292,293,294)	31.3 (26.0 to 36.5)	37.8 (32.5 to 43.2)	30.9 (25.7 to 36.0)
Week 28 (n = 283,287,284)	28.3 (23.1 to 33.5)	32.6 (27.4 to 37.8)	35.0 (29.7 to 40.4)
Week 32 (n = 267,268,275)	33.7 (28.0 to 39.3)	38.8 (33.2 to 44.4)	31.0 (25.8 to 36.2)
Week 36 (n = 268,268,268)	29.6 (24.1 to 35.0)	42.4 (36.8 to 48.1)	35.6 (30.0 to 41.1)
Week 40 (n = 275,269,263)	32.9 (27.4 to 38.5)	40.4 (34.7 to 46.2)	33.8 (28.2 to 39.4)
Week 44 (n = 268,269,266)	32.1 (26.5 to 37.7)	39.7 (34.1 to 45.3)	39.9 (34.2 to 45.7)
Week 48 (n = 264,266,266)	35.7 (30.0 to 41.5)	41.8 (36.1 to 47.6)	41.7 (36.0 to 47.4)
Week 52 (n = 264,267,253)	35.7 (29.9 to 41.4)	40.2 (34.5 to 45.8)	41.7 (35.8 to 47.6)
Week 56 (n = 260,263,256)	43.1 (37.1 to 49.1)	42.6 (36.7 to 48.4)	35.7 (30.1 to 41.4)
Week 60 (n = 270,261,261)	39.5 (33.7 to 45.3)	45.0 (39.1 to 51.0)	40.6 (34.8 to 46.3)
Week 64 (n = 259,263,263)	42.1 (36.1 to 48.1)	44.0 (38.2 to 49.8)	37.9 (32.1 to 43.7)
Week 68 (n = 251,257,253)	42.2 (36.2 to 48.2)	45.6 (39.7 to 51.6)	40.3 (34.5 to 46.2)
Week 72 (n = 253,257,251)	39.8 (33.9 to 45.8)	40.5 (34.8 to 46.2)	37.7 (31.8 to 43.6)
Week 76 (n = 247,253,251)	42.2 (36.1 to 48.4)	47.7 (41.8 to 53.5)	42.9 (36.8 to 49.0)
Week 80 (n = 247,259,251)	42.9 (36.8 to 49.0)	44.8 (39.0 to 50.5)	41.9 (35.9 to 47.8)
Week 84 (n = 248,260,252)	42.4 (36.3 to 48.5)	43.0 (37.2 to 48.7)	42.9 (36.9 to 48.9)
Week 88 (n = 245,256,247)	41.2 (35.1 to 47.3)	41.7 (36.1 to 47.4)	40.0 (34.1 to 46.0)
Week 92 (n = 248,258,248)	42.5 (36.4 to 48.5)	43.6 (37.8 to 49.4)	42.7 (36.7 to 48.7)
Week 96 (n = 242,259,245)	44.9 (38.7 to 51.1)	42.4 (36.6 to 48.1)	42.7 (36.6 to 48.7)
Week 100 (n = 254,258,247)	43.5 (37.5 to 49.6)	41.8 (36.1 to 47.5)	44.7 (38.6 to 50.8)

No statistical analyses for this end point

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population

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End point title

Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 234,241,236)	9.8 (6.0 to 13.5)	17.0 (12.4 to 21.6)	15.2 (10.7 to 19.8)
Week 8 (n = 232,240,234)	16.0 (11.3 to 20.7)	20.9 (16.1 to 25.7)	22.2 (16.9 to 27.4)
Week 12 (n = 230,235,235)	19.2 (14.1 to 24.2)	25.6 (20.3 to 30.9)	28.5 (22.9 to 34.1)
Week 16 (n = 222,229,232)	24.9 (19.2 to 30.5)	29.5 (23.8 to 35.2)	27.9 (22.2 to 33.6)
Week 20 (n = 223,227,229)	31.0 (25.0 to 37.0)	30.4 (24.6 to 36.1)	30.6 (24.8 to 36.4)
Week 24 (n = 219,228,228)	32.5 (26.3 to 38.7)	38.2 (32.1 to 44.3)	33.3 (27.3 to 39.4)
Week 28 (n = 212,224,217)	26.9 (20.9 to 32.9)	32.0 (26.2 to 37.8)	38.5 (32.2 to 44.8)
Week 32 (n = 195,205,209)	33.3 (26.7 to 39.9)	40.5 (34.0 to 46.9)	35.4 (29.0 to 41.7)
Week 36 (n = 194,205,205)	29.5 (23.1 to 36.0)	44.8 (38.3 to 51.3)	38.4 (31.9 to 44.8)
Week 40 (n = 202,204,200)	31.5 (25.1 to 37.9)	41.1 (34.5 to 47.7)	37.1 (30.4 to 43.7)
Week 44 (n = 199,209,202)	31.1 (24.7 to 37.6)	42.9 (36.4 to 49.5)	42.7 (36.0 to 49.4)
Week 48 (n = 195,210,203)	37.5 (30.7 to 44.3)	41.9 (35.3 to 48.5)	44.9 (38.2 to 51.6)
Week 52 (n = 197,209,196)	35.5 (28.9 to 42.2)	39.2 (32.8 to 45.6)	43.8 (36.9 to 50.6)
Week 56 (n = 194,207,198)	43.3 (36.3 to 50.3)	43.1 (36.5 to 49.7)	38.9 (32.2 to 45.5)
Week 60 (n = 200,198,199)	39.4 (32.6 to 46.2)	46.7 (39.9 to 53.5)	43.6 (36.8 to 50.4)
Week 64 (n = 191,202,200)	43.0 (36.0 to 50.0)	46.4 (39.8 to 53.1)	38.7 (32.0 to 45.3)
Week 68 (n = 187,197,193)	43.7 (36.6 to 50.7)	47.9 (41.1 to 54.7)	42.2 (35.4 to 49.0)
Week 72 (n = 186,196,189)	40.7 (33.7 to 47.8)	42.1 (35.5 to 48.7)	39.3 (32.5 to 46.2)
Week 76 (n = 180,195,189)	44.6 (37.3 to 51.8)	49.9 (43.3 to 56.6)	43.8 (36.8 to 50.8)
Week 80 (n = 177,203,190)	44.6 (37.3 to 51.8)	46.6 (40.1 to 53.2)	46.1 (39.1 to 53.1)
Week 84 (n = 181,203,192)	42.7 (35.6 to 49.9)	45.2 (38.6 to 51.7)	45.7 (38.7 to 52.7)
Week 88 (n = 179,196,185)	41.3 (34.2 to 48.5)	42.7 (36.3 to 49.2)	42.5 (35.5 to 49.6)
Week 92 (n = 180,199,188)	43.4 (36.3 to 50.6)	45.5 (38.9 to 52.1)	43.9 (36.9 to 50.8)
Week 96 (n = 174,201,187)	46.7 (39.3 to 54.1)	43.6 (37.2 to 50.1)	44.7 (37.7 to 51.8)
Week 100 (n = 185,199,186)	44.1 (37.0 to 51.3)	44.4 (37.9 to 50.9)	45.8 (38.8 to 52.9)

No statistical analyses for this end point

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

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End point title

Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

End point description

BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥69 vs. <69 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, average of Weeks 48, 52, and 56

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	271	276	276	200	215	212
Units: Percentage of participants
number (confidence interval 95%)	71.6 (66.5 to 76.6)	77.1 (72.4 to 81.8)	74.8 (69.9 to 79.6)	72.7 (66.9 to 78.5)	75.7 (70.3 to 81.1)	77.4 (72.2 to 82.7)

ITT: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

547

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-3.2

Confidence interval

level

95%

sides

2-sided

lower limit

-10.2

upper limit

3.8

ITT: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.3

upper limit

9.2

TN: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-12.6

upper limit

3.1

TN: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

427

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-8.9

upper limit

6.4

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥69 vs. <69 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 310,308,306)	53.3 (48.4 to 58.1)	60.0 (55.1 to 64.8)	57.5 (52.6 to 62.4)
Week 8 (n = 309,308,304)	60.0 (55.1 to 64.9)	65.5 (60.8 to 70.1)	66.1 (61.4 to 70.8)
Week 12 (n = 305,303,302)	64.4 (59.4 to 69.3)	69.3 (64.6 to 74.0)	68.8 (64.1 to 73.6)
Week 16 (n = 296,296,299)	66.1 (61.1 to 71.2)	70.6 (65.8 to 75.3)	74.7 (70.1 to 79.2)
Week 20 (n = 294,292,296)	70.3 (65.4 to 75.3)	69.7 (64.9 to 74.6)	70.3 (65.5 to 75.1)
Week 24 (n = 292,293,294)	71.0 (66.1 to 76.0)	76.0 (71.4 to 80.6)	71.0 (66.3 to 75.8)
Week 28 (n = 283,287,284)	71.5 (66.5 to 76.4)	74.5 (69.9 to 79.1)	75.1 (70.4 to 79.8)
Week 32 (n = 267,268,275)	71.4 (66.3 to 76.5)	74.1 (69.2 to 79.0)	74.9 (70.1 to 79.7)
Week 36 (n = 268,268,268)	71.8 (66.8 to 76.9)	79.4 (74.7 to 84.1)	73.2 (68.1 to 78.2)
Week 40 (n = 275,269,263)	69.3 (64.2 to 74.4)	75.1 (70.2 to 80.1)	73.6 (68.5 to 78.7)
Week 44 (n = 268,269,266)	70.6 (65.4 to 75.7)	77.7 (72.9 to 82.5)	73.4 (68.3 to 78.4)
Week 48 (n = 264,266,266)	73.4 (68.4 to 78.4)	78.3 (73.6 to 83.0)	72.7 (67.6 to 77.8)
Week 52 (n = 264,267,253)	69.3 (63.9 to 74.6)	76.6 (71.7 to 81.4)	75.2 (70.2 to 80.2)
Week 56 (n = 260,263,256)	74.9 (69.9 to 79.9)	79.5 (74.8 to 84.2)	72.2 (67.0 to 77.4)
Week 60 (n = 270,261,261)	71.8 (66.6 to 76.9)	76.6 (71.6 to 81.5)	75.9 (70.9 to 80.9)
Week 64 (n = 259,263,263)	74.9 (69.8 to 79.9)	76.2 (71.4 to 81.0)	71.4 (66.3 to 76.5)
Week 68 (n = 251,257,253)	74.4 (69.2 to 79.7)	78.0 (73.2 to 82.8)	73.9 (68.9 to 78.9)
Week 72 (n = 253,257,251)	73.9 (68.6 to 79.1)	76.8 (72.0 to 81.7)	71.0 (65.8 to 76.1)
Week 76 (n = 247,253,251)	72.6 (67.2 to 78.0)	77.0 (72.0 to 82.0)	76.0 (71.1 to 81.0)
Week 80 (n = 247,259,251)	74.6 (69.3 to 79.9)	77.5 (72.5 to 82.4)	73.8 (68.7 to 78.9)
Week 84 (n = 248,260,252)	73.7 (68.4 to 79.1)	77.2 (72.3 to 82.1)	77.3 (72.5 to 82.2)
Week 88 (n = 245,256,247)	72.2 (66.7 to 77.7)	76.2 (71.2 to 81.3)	73.3 (68.0 to 78.5)
Week 92 (n = 248,258,248)	75.3 (70.0 to 80.6)	78.4 (73.4 to 83.3)	77.4 (72.6 to 82.2)
Week 96 (n = 242,259,245)	75.9 (70.6 to 81.2)	74.3 (69.0 to 79.5)	73.4 (68.3 to 78.5)
Week 100 (n = 254,258,247)	75.9 (70.7 to 81.1)	70.3 (64.9 to 75.7)	75.7 (70.8 to 80.7)

No statistical analyses for this end point

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population

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End point title

Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of th percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥69 vs. <69 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 234,241,236)	55.7 (50.1 to 61.2)	60.4 (55.0 to 65.8)	60.4 (54.9 to 65.9)
Week 8 (n = 232,240,234)	62.0 (56.5 to 67.6)	66.5 (61.3 to 71.6)	69.6 (64.3 to 74.8)
Week 12 (n = 230,235,235)	66.2 (60.5 to 71.8)	69.3 (64.1 to 74.5)	70.6 (65.3 to 75.9)
Week 16 (n = 222,229,232)	68.5 (62.8 to 74.2)	68.5 (63.1 to 74.0)	75.8 (70.8 to 80.9)
Week 20 (n = 223,227,229)	72.7 (67.1 to 78.2)	67.8 (62.2 to 73.4)	72.0 (66.7 to 77.3)
Week 24 (n = 219,228,228)	73.7 (68.2 to 79.3)	74.5 (69.2 to 79.8)	72.6 (67.3 to 77.9)
Week 28 (n = 212,224,217)	73.7 (68.2 to 79.3)	73.1 (67.8 to 78.4)	77.0 (71.8 to 82.2)
Week 32 (n = 195,205,209)	71.8 (65.8 to 77.7)	72.4 (66.7 to 78.1)	75.8 (70.4 to 81.2)
Week 36 (n = 194,205,205)	74.7 (68.9 to 80.5)	79.4 (74.0 to 84.7)	73.4 (67.6 to 79.1)
Week 40 (n = 202,204,200)	70.6 (64.7 to 76.6)	74.6 (68.9 to 80.3)	75.8 (70.2 to 81.4)
Week 44 (n = 199,209,202)	71.1 (65.2 to 77.1)	76.9 (71.3 to 82.4)	76.4 (70.8 to 82.0)
Week 48 (n = 195,210,203)	74.3 (68.6 to 80.0)	75.7 (70.2 to 81.2)	75.3 (69.8 to 80.9)
Week 52 (n = 197,209,196)	71.7 (65.6 to 77.7)	74.4 (68.7 to 80.1)	77.5 (71.9 to 83.0)
Week 56 (n = 194,207,198)	76.9 (71.3 to 82.5)	77.9 (72.4 to 83.4)	74.0 (68.2 to 79.7)
Week 60 (n = 200,198,199)	73.4 (67.5 to 79.3)	75.2 (69.4 to 81.0)	78.3 (72.8 to 83.8)
Week 64 (n = 191,202,200)	77.0 (71.2 to 82.7)	75.5 (69.9 to 81.0)	74.4 (68.9 to 80.0)
Week 68 (n = 187,197,193)	77.6 (71.7 to 83.5)	77.9 (72.4 to 83.3)	75.5 (69.9 to 81.0)
Week 72 (n = 186,196,189)	76.7 (70.7 to 82.6)	75.9 (70.3 to 81.4)	74.5 (68.9 to 80.1)
Week 76 (n = 180,195,189)	72.7 (66.3 to 79.1)	75.8 (70.1 to 81.5)	78.0 (72.6 to 83.3)
Week 80 (n = 177,203,190)	76.4 (70.2 to 82.6)	76.8 (71.2 to 82.5)	76.5 (70.9 to 82.1)
Week 84 (n = 181,203,192)	75.7 (69.5 to 81.9)	77.8 (72.3 to 83.3)	77.8 (72.4 to 83.2)
Week 88 (n = 179,196,185)	71.8 (65.2 to 78.3)	75.7 (69.9 to 81.5)	76.0 (70.1 to 81.9)
Week 92 (n = 180,199,188)	75.9 (69.7 to 82.1)	77.7 (71.9 to 83.4)	79.9 (74.7 to 85.2)
Week 96 (n = 174,201,187)	77.3 (71.1 to 83.4)	73.5 (67.4 to 79.5)	75.5 (69.9 to 81.2)
Week 100 (n = 185,199,186)	77.6 (71.6 to 83.6)	70.8 (64.6 to 76.9)	77.0 (71.4 to 82.5)

No statistical analyses for this end point

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

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End point title

Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

End point description

End point type

Secondary

End point timeframe

Baseline, average of Weeks 48, 52, and 56

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	271	276	276	200	215	212
Units: Percentage of participants
number (confidence interval 95%)	2.3 (0.5 to 4.1)	1.9 (0.3 to 3.5)	1.7 (0.3 to 3.2)	2.6 (0.4 to 4.8)	1.9 (0.1 to 3.7)	1.8 (0.1 to 3.5)

ITT: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

547

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

2.9

TN: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

3.6

TN: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

427

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

2.5

ITT: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

2.3

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population

Top of page

End point title

Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement invisual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 310,308,306)	1.9 (0.4 to 3.4)	2.6 (0.9 to 4.3)	1.6 (0.2 to 3.0)
Week 8 (n = 309,308,304)	2.0 (0.4 to 3.5)	3.0 (1.1 to 4.8)	2.0 (0.4 to 3.5)
Week 12 (n = 305,303,302)	1.6 (0.2 to 3.0)	2.0 (0.5 to 3.5)	1.6 (0.2 to 3.0)
Week 16 (n = 296,296,299)	0.7 (0.0 to 1.6)	2.1 (0.5 to 3.7)	1.6 (0.2 to 3.0)
Week 20 (n = 294,292,296)	1.3 (0.0 to 2.7)	1.7 (0.3 to 3.2)	1.7 (0.2 to 3.1)
Week 24 (n = 292,293,294)	0.7 (0.0 to 1.6)	1.7 (0.3 to 3.2)	1.7 (0.3 to 3.1)
Week 28 (n = 283,287,284)	1.4 (0.1 to 2.8)	1.4 (0.1 to 2.8)	1.4 (0.1 to 2.7)
Week 32 (n = 267,268,275)	1.1 (0.0 to 2.4)	1.2 (0.0 to 2.4)	1.8 (0.2 to 3.3)
Week 36 (n = 268,268,268)	1.6 (0.1 to 3.1)	1.6 (0.1 to 3.1)	1.5 (0.1 to 3.0)
Week 40 (n = 275,269,263)	1.5 (0.1 to 3.0)	2.3 (0.5 to 4.1)	1.5 (0.1 to 2.9)
Week 44 (n = 268,269,266)	3.1 (1.0 to 5.2)	1.9 (0.3 to 3.6)	1.4 (0.1 to 2.8)
Week 48 (n = 264,266,266)	1.6 (0.1 to 3.1)	2.3 (0.5 to 4.1)	1.8 (0.3 to 3.3)
Week 52 (n = 264,267,253)	2.0 (0.3 to 3.8)	1.5 (0.1 to 3.0)	1.5 (0.1 to 2.9)
Week 56 (n = 260,263,256)	1.5 (0.0 to 3.0)	1.6 (0.1 to 3.1)	1.9 (0.3 to 3.5)
Week 60 (n = 270,261,261)	1.9 (0.3 to 3.5)	1.2 (0.0 to 2.5)	1.4 (0.1 to 2.8)
Week 64 (n = 259,263,263)	1.2 (0.0 to 2.6)	2.5 (0.6 to 4.3)	1.8 (0.2 to 3.3)
Week 68 (n = 251,257,253)	1.3 (0.0 to 2.7)	2.4 (0.6 to 4.3)	1.8 (0.3 to 3.4)
Week 72 (n = 253,257,251)	1.3 (0.0 to 2.7)	1.6 (0.1 to 3.1)	1.5 (0.1 to 2.9)
Week 76 (n = 247,253,251)	0.9 (0.0 to 2.1)	1.6 (0.1 to 3.2)	3.4 (1.3 to 5.6)
Week 80 (n = 247,259,251)	0.9 (0.0 to 2.1)	2.0 (0.3 to 3.8)	3.0 (1.0 to 5.0)
Week 84 (n = 248,260,252)	0.9 (0.0 to 2.1)	1.6 (0.1 to 3.2)	1.0 (0.0 to 2.2)
Week 88 (n = 245,256,247)	1.3 (0.0 to 2.7)	1.7 (0.1 to 3.2)	2.0 (0.3 to 3.8)
Week 92 (n = 248,258,248)	2.2 (0.3 to 4.0)	2.1 (0.4 to 3.9)	2.8 (0.8 to 4.8)
Week 96 (n = 242,259,245)	1.7 (0.1 to 3.4)	2.1 (0.3 to 3.8)	0.9 (0.0 to 2.1)
Week 100 (n = 254,258,247)	2.5 (0.5 to 4.5)	2.1 (0.3 to 3.8)	1.2 (0.0 to 2.6)

No statistical analyses for this end point

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, Treatment-Naive Population

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End point title

Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, Treatment-Naive Population

End point description

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 234,241,236)	1.7 (0.1 to 3.3)	2.9 (0.8 to 4.9)	1.3 (0.0 to 2.7)
Week 8 (n = 232,240,234)	2.2 (0.3 to 4.0)	3.3 (1.1 to 5.5)	2.1 (0.3 to 3.9)
Week 12 (n = 230,235,235)	1.3 (0.0 to 2.7)	2.1 (0.3 to 3.9)	1.7 (0.1 to 3.3)
Week 16 (n = 222,229,232)	0.5 (0.0 to 1.3)	2.2 (0.3 to 4.0)	1.7 (0.1 to 3.3)
Week 20 (n = 223,227,229)	1.3 (0.0 to 2.8)	1.7 (0.1 to 3.4)	1.7 (0.1 to 3.4)
Week 24 (n = 219,228,228)	0.5 (0.0 to 1.4)	1.7 (0.1 to 3.4)	1.3 (0.0 to 2.7)
Week 28 (n = 212,224,217)	1.0 (0.0 to 2.4)	1.3 (0.0 to 2.9)	1.3 (0.0 to 2.8)
Week 32 (n = 195,205,209)	1.1 (0.0 to 2.5)	1.0 (0.0 to 2.3)	1.9 (0.1 to 3.7)
Week 36 (n = 194,205,205)	1.7 (0.0 to 3.5)	1.0 (0.0 to 2.4)	1.5 (0.0 to 3.1)
Week 40 (n = 202,204,200)	1.6 (0.0 to 3.3)	2.0 (0.1 to 3.9)	1.4 (0.0 to 3.0)
Week 44 (n = 199,209,202)	2.7 (0.4 to 4.9)	2.0 (0.1 to 3.8)	1.4 (0.0 to 2.9)
Week 48 (n = 195,210,203)	1.6 (0.0 to 3.4)	2.4 (0.3 to 4.5)	1.9 (0.1 to 3.7)
Week 52 (n = 197,209,196)	2.7 (0.4 to 5.0)	1.9 (0.1 to 3.8)	1.4 (0.0 to 3.0)
Week 56 (n = 194,207,198)	1.0 (0.0 to 2.5)	1.5 (0.0 to 3.1)	2.0 (0.1 to 3.9)
Week 60 (n = 200,198,199)	2.1 (0.1 to 4.1)	1.0 (0.0 to 2.4)	1.9 (0.1 to 3.8)
Week 64 (n = 191,202,200)	1.6 (0.0 to 3.5)	2.0 (0.1 to 4.0)	1.9 (0.1 to 3.7)
Week 68 (n = 187,197,193)	1.1 (0.0 to 2.7)	1.6 (0.0 to 3.3)	1.9 (0.1 to 3.7)
Week 72 (n = 186,196,189)	1.7 (0.0 to 3.6)	1.0 (0.0 to 2.4)	1.4 (0.0 to 3.0)
Week 76 (n = 180,195,189)	1.2 (0.0 to 2.8)	1.5 (0.0 to 3.2)	3.5 (1.0 to 6.0)
Week 80 (n = 177,203,190)	1.2 (0.0 to 2.8)	2.0 (0.1 to 4.0)	3.5 (1.0 to 6.0)
Week 84 (n = 181,203,192)	1.2 (0.0 to 2.8)	1.0 (0.0 to 2.4)	1.4 (0.0 to 2.9)
Week 88 (n = 179,196,185)	1.7 (0.0 to 3.7)	1.0 (0.0 to 2.4)	2.1 (0.1 to 4.2)
Week 92 (n = 180,199,188)	2.4 (0.1 to 4.6)	1.5 (0.0 to 3.3)	2.6 (0.3 to 4.9)
Week 96 (n = 174,201,187)	1.3 (0.0 to 3.0)	2.1 (0.1 to 4.0)	0.6 (0.0 to 1.7)
Week 100 (n = 185,199,186)	2.3 (0.1 to 4.5)	2.1 (0.1 to 4.1)	1.1 (0.0 to 2.6)

No statistical analyses for this end point

Secondary: Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

End point description

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 52, and 96

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 279,291,281)	36.7 (31.2 to 42.3)	35.0 (29.6 to 40.5)	28.9 (23.9 to 34.0)
Week 52 (n = 249,253,236)	46.2 (40.0 to 52.3)	42.3 (36.4 to 48.3)	35.4 (29.6 to 41.2)
Week 96 (n = 220,234,221)	51.4 (44.8 to 57.9)	42.8 (36.6 to 49.0)	42.2 (35.9 to 48.5)

No statistical analyses for this end point

Secondary: Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

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End point title

Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

End point description

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 52, and 96

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 209,225,219)	39.3 (32.7 to 45.8)	39.5 (33.2 to 45.9)	33.3 (27.1 to 39.4)
Week 52 (n = 182,196,184)	49.5 (42.3 to 56.8)	47.4 (40.5 to 54.4)	42.3 (35.3 to 49.3)
Week 96 (n = 159,178,169)	52.3 (44.6 to 60.1)	47.0 (39.7 to 54.2)	49.1 (41.7 to 56.6)

No statistical analyses for this end point

Secondary: Percentage of Participants with a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants with a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

End point description

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 52, and 96

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 279,291,281)	12.7 (8.8 to 16.5)	12.8 (9.0 to 16.6)	10.3 (6.8 to 13.8)
Week 52 (n = 249,253,236)	17.0 (12.3 to 21.6)	15.3 (10.9 to 19.8)	14.2 (10.0 to 18.5)
Week 96 (n = 220,234,221)	22.4 (16.9 to 27.8)	14.6 (10.0 to 19.1)	20.9 (15.8 to 26.0)

No statistical analyses for this end point

Secondary: Percentage of Participants with a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

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End point title

Percentage of Participants with a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

End point description

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 52, and 96

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 209,225,219)	14.4 (9.7 to 19.1)	15.1 (10.4 to 19.8)	10.4 (6.4 to 14.4)
Week 52 (n = 182,196,184)	19.5 (13.7 to 25.2)	17.4 (12.1 to 22.8)	16.4 (11.2 to 21.6)
Week 96 (n = 159,178,169)	23.9 (17.3 to 30.5)	17.1 (11.5 to 22.6)	25.3 (18.9 to 31.6)

No statistical analyses for this end point

Secondary: Percentage of Participants with a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants with a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

End point description

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 52, and 96

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 279,291,281)	3.6 (1.4 to 5.8)	3.5 (1.4 to 5.6)	3.9 (1.7 to 6.2)
Week 52 (n = 249,253,236)	5.8 (2.9 to 8.7)	4.9 (2.2 to 7.7)	4.5 (1.9 to 7.0)
Week 96 (n = 220,234,221)	5.9 (2.8 to 9.0)	5.8 (2.8 to 8.8)	6.0 (3.0 to 9.0)

No statistical analyses for this end point

Secondary: Percentage of Participants with a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

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End point title

Percentage of Participants with a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

End point description

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 52, and 96

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 209,225,219)	3.9 (1.3 to 6.4)	3.5 (1.1 to 5.9)	3.6 (1.2 to 6.1)
Week 52 (n = 182,196,184)	6.2 (2.7 to 9.7)	5.1 (2.0 to 8.3)	4.2 (1.4 to 7.0)
Week 96 (n = 159,178,169)	7.0 (3.0 to 11.0)	6.8 (3.1 to 10.5)	6.3 (2.8 to 9.8)

No statistical analyses for this end point

Secondary: Percentage of Participants Without Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed New PDR at Week 52, ITT and Treatment-Naive Populations

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End point title

Percentage of Participants Without Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed New PDR at Week 52, ITT and Treatment-Naive Populations

End point description

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). PDR was defined as an ETDRS DRSS score of ≥61 on the 7-field/4-wide field color fundus photographs assessment by a central reading center. The weighted percentages of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% CI is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	219	224	214	158	172	168
Units: Percentage of participants
number (confidence interval 95%)	0.9 (0.0 to 2.2)	0.9 (0.0 to 2.2)	0.5 (0.0 to 1.4)	0.0 (0.0 to 0.0)	1.2 (0.0 to 2.8)	0.6 (0.0 to 1.9)

ITT: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

433

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

ITT: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

438

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

TN: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

326

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.6

TN: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

340

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

2.5

Secondary: Percentage of Participants Without High-Risk Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed High-Risk PDR at Week 52, ITT and Treatment-Naive Populations

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End point title

Percentage of Participants Without High-Risk Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed High-Risk PDR at Week 52, ITT and Treatment-Naive Populations

End point description

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced PDR. High-risk PDR was defined as an ETDRS DRSS score of ≥71 on the 7-field/4-wide field color fundus photographs assessment by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% CI is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	237	241	227	173	187	177
Units: Percentage of participants
number (confidence interval 95%)	0.4 (0.0 to 1.2)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)

ITT: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

464

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

1.2

ITT: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

468

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

TN: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

TN: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

364

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Secondary: Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population

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End point title

Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population ^[13]

End point description

End point type

Secondary

End point timeframe

Week 52

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only applicable to participants who were randomized to Arm B: Faricimab 6 mg Personalized Treatment Interval (PTI) and had not discontinued the study prior to Week 52.

End point values	B: Faricimab 6 mg PTI
Number of subjects analysed	286
Units: Percentage of participants
number (confidence interval 95%)
Once Every 4 Weeks	10.8 (7.2 to 14.4)
Once Every 8 Weeks	15.4 (11.2 to 19.6)
Once Every 12 Weeks	21.0 (16.3 to 25.7)
Once Every 16 Weeks	52.8 (47.0 to 58.6)

No statistical analyses for this end point

Secondary: Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population

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End point title

Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population

End point description

End point type

Secondary

End point timeframe

Week 52

End point values	B: Faricimab 6 mg PTI, TN Population
Number of subjects analysed	222
Units: Percentage of participants
number (confidence interval 95%)
Once Every 4 Weeks	9.0 (5.2 to 12.8)
Once Every 8 Weeks	14.4 (9.8 to 19.0)
Once Every 12 Weeks	22.1 (16.6 to 27.5)
Once Every 16 Weeks	54.5 (47.9 to 61.1)

No statistical analyses for this end point

Secondary: Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population

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End point title

Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population ^[14]

End point description

End point type

Secondary

End point timeframe

Week 96

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only applicable to participants who were randomized to Arm B: Faricimab 6 mg Personalized Treatment Interval (PTI) and had not discontinued the study prior to Week 96.

End point values	B: Faricimab 6 mg PTI
Number of subjects analysed	270
Units: Percentage of participants
number (confidence interval 95%)
Once Every 4 Weeks	7.0 (4.0 to 10.1)
Once Every 8 Weeks	14.8 (10.6 to 19.1)
Once Every 12 Weeks	18.1 (13.5 to 22.8)
Once Every 16 Weeks	60.0 (54.1 to 65.9)

No statistical analyses for this end point

Secondary: Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population

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End point title

Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population

End point description

End point type

Secondary

End point timeframe

Week 96

End point values	B: Faricimab 6 mg PTI, TN Population
Number of subjects analysed	208
Units: Percentage of participants
number (confidence interval 95%)
Once Every 4 Weeks	7.2 (3.7 to 10.7)
Once Every 8 Weeks	11.1 (6.8 to 15.3)
Once Every 12 Weeks	16.8 (11.7 to 21.9)
Once Every 16 Weeks	64.9 (58.4 to 71.4)

No statistical analyses for this end point

Secondary: Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 52 who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations

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End point title

Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 52 who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations ^[15]

End point description

End point type

Secondary

End point timeframe

From start of PTI (Week 12 or later) until Week 52

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only applicable to participants who were randomized to Arm B: Faricimab 6 mg Personalized Treatment Interval (PTI) and had not discontinued the study prior to Week 52.

End point values	B: Faricimab 6 mg PTI	B: Faricimab 6 mg PTI, TN Population
Number of subjects analysed	286	222
Units: Percentage of participants
number (confidence interval 95%)	67.8 (62.4 to 73.3)	71.6 (65.7 to 77.6)

No statistical analyses for this end point

Secondary: Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 96 who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations

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End point title

Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 96 who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations ^[16]

End point description

End point type

Secondary

End point timeframe

From start of PTI (Week 12 or later) until Week 96

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only applicable to participants who were randomized to Arm B: Faricimab 6 mg Personalized Treatment Interval (PTI) and had not discontinued the study prior to Week 96.

End point values	B: Faricimab 6 mg PTI	B: Faricimab 6 mg PTI, TN Population
Number of subjects analysed	270	208
Units: Percentage of participants
number (confidence interval 95%)	60.4 (54.5 to 66.2)	64.4 (57.9 to 70.9)

No statistical analyses for this end point

Secondary: Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

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End point title

Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

End point description

Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

From Baseline through Week 56

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	315	313	312	238	245	242
Units: microns
arithmetic mean (confidence interval 95%)	-206.6 (-214.7 to -198.4)	-196.5 (-204.7 to -188.4)	-170.3 (-178.5 to -162.2)	-204.6 (-213.5 to -195.7)	-197.5 (-206.2 to -188.8)	-173.6 (-182.3 to -164.8)

ITT: Arm A vs. Arm C

Statistical analysis description

This is the adjusted mean difference for Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

627

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted mean difference

Point estimate

-36.2

Confidence interval

level

95%

sides

2-sided

lower limit

-47.8

upper limit

-24.7

Variability estimate

Standard error of the mean

Dispersion value

5.88

TN: Arm A vs. Arm C

Statistical analysis description

This is the adjusted mean difference for Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

480

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted mean difference

Point estimate

-31.1

Confidence interval

level

95%

sides

2-sided

lower limit

-43.6

upper limit

-18.6

Variability estimate

Standard error of the mean

Dispersion value

6.35

TN: Arm B vs. Arm C

Statistical analysis description

This is the adjusted mean difference for Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W in the Treatment-Naive Population.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

487

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted mean difference

Point estimate

-23.9

Confidence interval

level

95%

sides

2-sided

lower limit

-36.2

upper limit

-11.6

Variability estimate

Standard error of the mean

Dispersion value

6.28

ITT: Arm B vs. Arm C

Statistical analysis description

This is the adjusted mean difference for Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W in the ITT Population.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

625

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted mean difference

Point estimate

-26.2

Confidence interval

level

95%

sides

2-sided

lower limit

-37.7

upper limit

-14.7

Variability estimate

Standard error of the mean

Dispersion value

5.86

Secondary: Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population

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End point title

Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: microns
arithmetic mean (confidence interval 95%)
Week 4	-118.4 (-128.5 to -108.2)	-124.9 (-135.0 to -114.8)	-111.0 (-121.2 to -100.8)
Week 8	-145.9 (-155.2 to -136.5)	-149.6 (-159.0 to -140.3)	-130.9 (-140.4 to -121.5)
Week 12	-165.6 (-174.3 to -156.9)	-168.4 (-177.1 to -159.8)	-144.7 (-153.4 to -136.0)
Week 16	-177.6 (-186.0 to -169.2)	-182.1 (-190.4 to -173.7)	-152.7 (-161.1 to -144.3)
Week 20	-184.6 (-193.2 to -176.1)	-174.6 (-183.1 to -166.0)	-159.0 (-167.6 to -150.4)
Week 24	-196.4 (-204.8 to -188.0)	-192.8 (-201.2 to -184.3)	-146.3 (-154.7 to -137.8)
Week 28	-174.6 (-184.4 to -164.9)	-193.7 (-203.4 to -184.0)	-163.8 (-173.6 to -154.0)
Week 32	-200.2 (-209.4 to -191.0)	-181.6 (-190.8 to -172.4)	-147.2 (-156.4 to -138.0)
Week 36	-179.4 (-188.9 to -169.8)	-201.0 (-210.6 to -191.5)	-166.0 (-175.7 to -156.4)
Week 40	-205.1 (-214.5 to -195.7)	-193.5 (-203.0 to -184.1)	-153.9 (-163.4 to -144.4)
Week 44	-187.5 (-197.4 to -177.5)	-189.2 (-199.1 to -179.3)	-172.6 (-182.6 to -162.6)
Week 48	-209.7 (-218.6 to -200.8)	-194.8 (-203.7 to -185.8)	-163.2 (-172.2 to -154.3)
Week 52	-191.0 (-200.6 to -181.4)	-193.0 (-202.6 to -183.4)	-179.2 (-188.9 to -169.5)
Week 56	-212.4 (-221.5 to -203.4)	-200.3 (-209.3 to -191.2)	-164.4 (-173.5 to -155.2)
Week 60	-197.8 (-207.4 to -188.2)	-196.3 (-205.9 to -186.6)	-182.0 (-191.7 to -172.3)
Week 64	-214.9 (-224.0 to -205.9)	-199.9 (-208.9 to -190.8)	-171.5 (-180.6 to -162.4)
Week 68	-201.1 (-210.0 to -192.3)	-200.9 (-209.7 to -192.1)	-186.8 (-195.7 to -177.9)
Week 72	-216.2 (-224.9 to -207.6)	-201.6 (-210.3 to -193.0)	-182.3 (-191.1 to -173.6)
Week 76	-206.0 (-215.1 to -197.0)	-200.7 (-209.8 to -191.7)	-188.4 (-197.6 to -179.3)
Week 80	-219.1 (-227.7 to -210.5)	-203.2 (-211.7 to -194.6)	-184.5 (-193.2 to -175.9)
Week 84	-211.8 (-221.1 to -202.5)	-204.9 (-214.1 to -195.7)	-186.2 (-195.5 to -176.9)
Week 88	-218.6 (-228.0 to -209.3)	-204.1 (-213.4 to -194.8)	-183.7 (-193.1 to -174.3)
Week 92	-210.9 (-220.1 to -201.7)	-202.4 (-211.4 to -193.3)	-193.9 (-203.2 to -184.7)
Week 96	-224.0 (-232.9 to -215.1)	-203.8 (-212.6 to -195.1)	-194.7 (-203.6 to -185.8)
Week 100	-213.1 (-221.8 to -204.3)	-207.3 (-216.0 to -198.6)	-200.2 (-209.0 to -191.4)

No statistical analyses for this end point

Secondary: Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population

Top of page

End point title

Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population

End point description

Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (<64 vs. ≥64 letters), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	238	245	242
Units: microns
arithmetic mean (confidence interval 95%)
Week 4	-116.1 (-127.0 to -105.2)	-121.5 (-132.1 to -110.9)	-110.1 (-120.9 to -99.3)
Week 8	-142.9 (-153.0 to -132.8)	-147.4 (-157.3 to -137.5)	-131.5 (-141.5 to -121.5)
Week 12	-162.8 (-171.9 to -153.6)	-166.7 (-175.7 to -157.8)	-147.4 (-156.4 to -138.3)
Week 16	-175.1 (-183.8 to -166.3)	-181.7 (-190.3 to -173.1)	-155.9 (-164.5 to -147.2)
Week 20	-182.9 (-192.0 to -173.8)	-178.1 (-187.0 to -169.2)	-161.6 (-170.6 to -152.6)
Week 24	-194.2 (-203.4 to -184.9)	-191.1 (-200.2 to -182.0)	-149.7 (-158.9 to -140.6)
Week 28	-177.4 (-188.1 to -166.7)	-194.0 (-204.4 to -183.5)	-167.5 (-178.0 to -156.9)
Week 32	-196.4 (-206.6 to -186.2)	-183.7 (-193.7 to -173.8)	-150.2 (-160.3 to -140.2)
Week 36	-181.9 (-191.9 to -171.9)	-203.6 (-213.3 to -193.8)	-168.7 (-178.6 to -158.9)
Week 40	-198.9 (-209.7 to -188.1)	-192.1 (-202.8 to -181.4)	-157.4 (-168.2 to -146.5)
Week 44	-187.3 (-198.5 to -176.1)	-189.3 (-200.2 to -178.3)	-172.9 (-184.0 to -161.8)
Week 48	-207.3 (-217.3 to -197.3)	-194.9 (-204.7 to -185.1)	-165.0 (-174.9 to -155.1)
Week 52	-191.1 (-201.7 to -180.5)	-196.2 (-206.5 to -185.9)	-181.1 (-191.6 to -170.5)
Week 56	-210.4 (-220.0 to -200.8)	-200.9 (-210.3 to -191.5)	-171.0 (-180.6 to -161.4)
Week 60	-195.0 (-205.6 to -184.4)	-198.0 (-208.4 to -187.5)	-185.1 (-195.6 to -174.5)
Week 64	-213.7 (-223.5 to -203.9)	-199.2 (-208.8 to -189.6)	-175.3 (-184.9 to -165.6)
Week 68	-201.5 (-211.2 to -191.7)	-201.7 (-211.2 to -192.1)	-189.1 (-198.8 to -179.5)
Week 72	-215.9 (-225.5 to -206.4)	-203.2 (-212.5 to -193.9)	-184.1 (-193.5 to -174.6)
Week 76	-204.8 (-214.8 to -194.9)	-202.1 (-211.8 to -192.4)	-189.8 (-199.7 to -180.0)
Week 80	-217.3 (-227.0 to -207.5)	-202.2 (-211.6 to -192.7)	-186.2 (-195.9 to -176.6)
Week 84	-211.0 (-221.6 to -200.4)	-202.9 (-213.2 to -192.7)	-185.7 (-196.1 to -175.2)
Week 88	-215.9 (-226.4 to -205.5)	-205.2 (-215.3 to -195.0)	-186.4 (-196.7 to -176.1)
Week 92	-208.8 (-218.9 to -198.7)	-202.2 (-212.0 to -192.5)	-195.9 (-205.9 to -186.0)
Week 96	-221.0 (-231.4 to -210.7)	-199.0 (-209.0 to -189.1)	-196.7 (-206.9 to -186.6)
Week 100	-213.4 (-222.7 to -204.1)	-206.7 (-215.7 to -197.7)	-201.3 (-210.5 to -192.1)

No statistical analyses for this end point

Secondary: Percentage of Participants with Absence of Diabetic Macular Edema in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

Top of page

End point title

Percentage of Participants with Absence of Diabetic Macular Edema in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

End point description

Absence of diabetic macular edema was defined as achieving a central subfield thickness (CST) of <325 microns in the study eye. CST was defined as the distance between the internal limiting membrane and Bruch's membrane. For each participant, an average CST value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Average of Weeks 48, 52, and 56

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W	A: Faricimab 6 mg Q8W, TN Population	B: Faricimab 6 mg PTI, TN Population	C: Aflibercept 2 mg Q8W, TN Population
Number of subjects analysed	272	276	275	201	215	211
Units: Percentage of participants
number (confidence interval 95%)	81.3 (76.8 to 85.9)	78.0 (73.1 to 82.8)	65.4 (59.9 to 70.8)	83.5 (78.4 to 88.5)	80.4 (75.1 to 85.7)	68.3 (62.1 to 74.4)

ITT: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.

Comparison groups

A: Faricimab 6 mg Q8W v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

547

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

8.9

upper limit

23.1

ITT: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the ITT Population.

Comparison groups

B: Faricimab 6 mg PTI v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

551

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

12.7

Confidence interval

level

95%

sides

2-sided

lower limit

5.4

upper limit

TN: Arm A vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm A: Faricimab 6 mg Q8W minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.

Comparison groups

A: Faricimab 6 mg Q8W, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

15.2

Confidence interval

level

95%

sides

2-sided

lower limit

7.3

upper limit

23.2

TN: Arm B vs. Arm C

Statistical analysis description

This is the difference in percentage of participants in Arm B: Faricimab 6 mg PTI minus Arm C: Aflibercept 2 mg Q8W for the Treatment-Naive Population.

Comparison groups

B: Faricimab 6 mg PTI, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

426

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

12.5

Confidence interval

level

95%

sides

2-sided

lower limit

4.4

upper limit

20.6

Secondary: Percentage of Participants with Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population

Top of page

End point title

Percentage of Participants with Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population

End point description

Absence of diabetic macular edema was defined as achieving a central subfield thickness of <325 microns in the study eye. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 309,307,303)	36.1 (30.8 to 41.4)	41.3 (35.9 to 46.8)	35.0 (29.7 to 40.4)
Week 8 (n = 309,309,303)	48.4 (42.9 to 54.0)	52.7 (47.2 to 58.2)	42.6 (37.1 to 48.2)
Week 12 (n = 303,301,301)	60.9 (55.4 to 66.4)	67.4 (62.1 to 72.6)	49.6 (44.0 to 55.2)
Week 16 (n = 293,293,299)	67.2 (61.8 to 72.5)	72.0 (66.9 to 77.0)	58.6 (53.1 to 64.1)
Week 20 (n = 294,291,294)	71.1 (65.9 to 76.2)	70.7 (65.6 to 75.8)	58.9 (53.4 to 64.5)
Week 24 (n = 290,289,291)	76.5 (71.7 to 81.4)	81.3 (76.8 to 85.8)	53.7 (48.1 to 59.4)
Week 28 (n = 281,284,283)	71.4 (66.2 to 76.5)	79.3 (74.6 to 84.0)	62.5 (57.0 to 68.0)
Week 32 (n = 265,265,270)	79.0 (74.2 to 83.8)	72.1 (66.8 to 77.4)	55.8 (50.1 to 61.5)
Week 36 (n = 265,266,264)	70.9 (65.6 to 76.1)	81.7 (77.1 to 86.3)	63.1 (57.4 to 68.8)
Week 40 (n = 275,267,262)	82.3 (77.9 to 86.7)	80.8 (76.1 to 85.5)	58.8 (53.0 to 64.7)
Week 44 (n = 266,268,266)	74.7 (69.6 to 79.9)	79.0 (74.3 to 83.8)	67.6 (62.1 to 73.1)
Week 48 (n = 263,261,261)	86.5 (82.5 to 90.5)	81.5 (76.8 to 86.1)	64.0 (58.3 to 69.7)
Week 52 (n = 262,266,252)	77.4 (72.4 to 82.4)	78.3 (73.4 to 83.1)	71.1 (65.6 to 76.7)
Week 56 (n = 260,262,251)	86.5 (82.4 to 90.7)	81.3 (76.6 to 86.0)	65.0 (59.2 to 70.8)
Week 60 (n = 267,260,257)	78.8 (74.0 to 83.6)	79.4 (74.6 to 84.3)	72.3 (66.9 to 77.7)
Week 64 (n = 257,260,261)	88.3 (84.4 to 92.2)	80.0 (75.2 to 84.8)	67.7 (62.1 to 73.3)
Week 68 (n = 250,256,249)	83.5 (79.0 to 88.1)	84.1 (79.7 to 88.5)	74.8 (69.4 to 80.1)
Week 72 (n = 254,256,245)	88.0 (84.0 to 92.0)	85.2 (81.0 to 89.5)	70.2 (64.5 to 75.9)
Week 76 (n = 247,251,245)	85.6 (81.3 to 89.8)	84.9 (80.5 to 89.2)	76.0 (70.7 to 81.2)
Week 80 (n = 249,257,248)	88.5 (84.5 to 92.4)	81.9 (77.3 to 86.6)	73.2 (67.7 to 78.7)
Week 84 (n = 247,258,250)	85.1 (80.7 to 89.5)	86.1 (82.0 to 90.3)	74.9 (69.5 to 80.3)
Week 88 (n = 246,253,245)	90.4 (86.8 to 94.0)	83.2 (78.7 to 87.7)	74.2 (68.7 to 79.6)
Week 92 (n = 247,257,244)	86.5 (82.3 to 90.7)	78.2 (73.2 to 83.3)	78.2 (73.1 to 83.3)
Week 96 (n = 239,257,245)	91.8 (88.4 to 95.3)	83.7 (79.2 to 88.2)	77.3 (72.1 to 82.4)
Week 100 (n = 247,257,243)	89.5 (85.7 to 93.4)	85.9 (81.7 to 90.1)	81.0 (76.1 to 86.0)

No statistical analyses for this end point

Secondary: Percentage of Participants with Retinal Dryness in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants with Retinal Dryness in the Study Eye Over Time, ITT Population

End point description

Retinal dryness was defined as achieving a central subfield thickness (ILM-BM) of <280 microns. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted estimates of the percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 309,307,303)	15.4 (11.5 to 19.4)	16.0 (12.0 to 19.9)	12.6 (8.9 to 16.3)
Week 8 (n = 309,309,303)	24.2 (19.6 to 28.8)	24.6 (19.9 to 29.3)	16.2 (12.1 to 20.3)
Week 12 (n = 303,301,301)	32.4 (27.3 to 37.5)	34.1 (28.9 to 39.4)	22.1 (17.4 to 26.7)
Week 16 (n = 293,293,299)	38.4 (33.0 to 43.9)	42.5 (36.9 to 48.0)	23.2 (18.5 to 27.9)
Week 20 (n = 294,291,294)	45.9 (40.3 to 51.5)	40.6 (35.0 to 46.1)	29.7 (24.5 to 34.8)
Week 24 (n = 290,289,291)	53.0 (47.3 to 58.7)	48.1 (42.4 to 53.8)	26.6 (21.6 to 31.6)
Week 28 (n = 281,284,283)	45.9 (40.1 to 51.7)	50.2 (44.4 to 55.9)	34.3 (28.8 to 39.8)
Week 32 (n = 265,265,270)	55.0 (49.1 to 60.8)	43.2 (37.3 to 49.0)	30.6 (25.1 to 36.1)
Week 36 (n = 265,266,264)	48.5 (42.5 to 54.5)	54.3 (48.4 to 60.3)	39.2 (33.4 to 45.1)
Week 40 (n = 275,267,262)	57.5 (51.8 to 63.2)	51.3 (45.3 to 57.3)	32.2 (26.7 to 37.7)
Week 44 (n = 266,268,266)	51.5 (45.7 to 57.4)	51.9 (46.1 to 57.8)	37.1 (31.4 to 42.8)
Week 48 (n = 263,261,261)	63.2 (57.4 to 69.0)	50.1 (44.2 to 56.0)	36.2 (30.4 to 42.0)
Week 52 (n = 262,266,252)	57.8 (51.9 to 63.7)	54.7 (48.7 to 60.6)	42.3 (36.2 to 48.4)
Week 56 (n = 260,262,251)	66.3 (60.6 to 72.0)	56.9 (51.0 to 62.9)	41.2 (35.1 to 47.2)
Week 60 (n = 267,260,257)	60.2 (54.4 to 66.0)	54.0 (48.0 to 60.0)	47.7 (41.6 to 53.7)
Week 64 (n = 257,260,261)	68.5 (62.8 to 74.1)	55.4 (49.4 to 61.3)	47.4 (41.3 to 53.4)
Week 68 (n = 250,256,249)	61.3 (55.3 to 67.3)	57.7 (51.7 to 63.8)	52.3 (46.1 to 58.5)
Week 72 (n = 254,256,245)	65.8 (60.1 to 71.5)	58.5 (52.6 to 64.3)	47.7 (41.4 to 53.9)
Week 76 (n = 247,251,245)	65.9 (60.1 to 71.8)	54.8 (48.6 to 60.9)	53.9 (47.7 to 60.1)
Week 80 (n = 249,257,248)	70.1 (64.5 to 75.8)	54.7 (48.7 to 60.6)	51.1 (44.8 to 57.3)
Week 84 (n = 247,258,250)	67.1 (61.3 to 72.9)	61.2 (55.5 to 67.0)	56.0 (49.9 to 62.2)
Week 88 (n = 246,253,245)	72.2 (66.7 to 77.7)	58.0 (52.1 to 64.0)	54.2 (48.0 to 60.5)
Week 92 (n = 247,257,244)	66.2 (60.5 to 72.0)	58.0 (52.2 to 63.8)	57.9 (51.7 to 64.0)
Week 96 (n = 239,257,245)	72.7 (67.2 to 78.2)	61.4 (55.6 to 67.2)	58.0 (51.8 to 64.2)
Week 100 (n = 247,257,243)	71.4 (65.9 to 76.8)	60.5 (54.5 to 66.4)	60.7 (54.5 to 66.8)

No statistical analyses for this end point

Secondary: Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population

End point description

Intraretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 289,293,298)	16.3 (12.0 to 20.5)	21.9 (17.1 to 26.6)	13.4 (9.6 to 17.3)
Week 48 (n = 262,261,263)	45.6 (39.7 to 51.6)	33.2 (27.5 to 38.9)	21.9 (17.0 to 26.9)
Week 52 (n = 262,261,249)	42.1 (36.3 to 47.9)	38.8 (32.9 to 44.7)	25.5 (20.2 to 30.8)
Week 56 (n = 254,256,254)	49.3 (43.3 to 55.3)	42.7 (36.7 to 48.7)	23.7 (18.5 to 28.9)
Week 92 (n = 242,251,241)	58.5 (52.3 to 64.7)	43.2 (37.1 to 49.3)	33.2 (27.4 to 39.1)
Week 96 (n = 232,254,241)	63.1 (57.0 to 69.2)	47.6 (41.5 to 53.7)	34.6 (28.7 to 40.6)
Week 100 (n = 238,251,237)	61.4 (55.2 to 67.5)	44.5 (38.4 to 50.7)	37.6 (31.5 to 43.6)

No statistical analyses for this end point

Secondary: Percentage of Participants with Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants with Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population

End point description

Subretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 294,294,297)	95.3 (92.9 to 97.7)	94.5 (92.0 to 97.1)	95.9 (93.7 to 98.2)
Week 48 (n = 263,266,261)	97.0 (95.0 to 99.0)	95.5 (93.1 to 97.9)	96.2 (93.8 to 98.5)
Week 52 (n = 263,264,252)	95.8 (93.3 to 98.2)	95.4 (92.9 to 97.9)	98.0 (96.2 to 99.7)
Week 56 (n = 258,260,255)	97.0 (95.0 to 99.0)	97.0 (95.0 to 99.0)	97.3 (95.3 to 99.3)
Week 92 (n = 246,255,243)	94.8 (92.1 to 97.6)	94.5 (91.7 to 97.3)	96.7 (94.5 to 99.0)
Week 96 (n = 237,256,242)	97.0 (94.8 to 99.1)	94.1 (91.3 to 97.0)	96.7 (94.5 to 98.9)
Week 100 (n = 246,257,244)	94.3 (91.4 to 97.2)	97.3 (95.4 to 99.2)	97.1 (95.0 to 99.2)

No statistical analyses for this end point

Secondary: Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population

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End point title

Percentage of Participants with Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population

End point description

Intraretinal fluid and subretinal fluid were measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 290,293,298)	15.9 (11.7 to 20.1)	21.9 (17.1 to 26.6)	13.1 (9.3 to 16.9)
Week 48 (n = 262,261,263)	45.2 (39.3 to 51.2)	32.4 (26.8 to 38.1)	21.9 (17.0 to 26.9)
Week 52 (n = 262,261,249)	42.1 (36.3 to 47.9)	38.0 (32.2 to 43.8)	25.5 (20.2 to 30.8)
Week 56 (n = 254,256,254)	47.0 (41.0 to 53.0)	42.4 (36.4 to 48.3)	23.7 (18.5 to 28.9)
Week 92 (n = 242,251,241)	57.2 (51.0 to 63.4)	41.3 (35.2 to 47.3)	32.0 (26.3 to 37.8)
Week 96 (n = 232,254,241)	62.4 (56.2 to 68.5)	46.0 (39.8 to 52.1)	34.2 (28.3 to 40.1)
Week 100 (n = 238,251,238)	59.3 (53.0 to 65.5)	43.8 (37.6 to 49.9)	37.4 (31.4 to 43.5)

No statistical analyses for this end point

Secondary: Change From Baseline in the National Eye Institute Visual Functioning Questionnaire–25 (NEI VFQ-25) Composite Score Over Time, ITT Population

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End point title

Change From Baseline in the National Eye Institute Visual Functioning Questionnaire–25 (NEI VFQ-25) Composite Score Over Time, ITT Population

End point description

The NEI VFQ-25 captures a patient’s perception of vision-related functioning and quality of life. The core measure includes 25 items that comprise 11 vision-related subscales and one item on general health. The composite score ranges from 0 to 100, with higher scores, or a positive change from baseline, indicating better vision-related functioning. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline NEI VFQ-25 Composite Score (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% CI is a rounding of 95.04% CI.

End point type

Secondary

End point timeframe

Baseline, Weeks 24, 52, and 100

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	315	313	312
Units: score on a scale
arithmetic mean (confidence interval 95%)
Week 24	6.0 (4.8 to 7.2)	6.9 (5.7 to 8.1)	6.0 (4.8 to 7.2)
Week 52	7.3 (5.9 to 8.6)	7.9 (6.6 to 9.3)	7.5 (6.1 to 8.9)
Week 100	8.0 (6.6 to 9.4)	7.4 (6.0 to 8.8)	7.6 (6.1 to 9.0)

No statistical analyses for this end point

Secondary: Percentage of Participants with at Least One Adverse Event

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End point title

Percentage of Participants with at Least One Adverse Event

End point description

This analysis of adverse events (AEs) includes both ocular and non-ocular (systemic) AEs. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. AEs of special interest included the following: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law; Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation.

End point type

Secondary

End point timeframe

From first dose of study drug through end of study (up to 2 years)

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	313	313	311
Units: Percentage of participants
number (not applicable)
Adverse Event (AE)	92.7	91.4	89.1
Serious AE (SAE)	35.5	37.4	29.9
AE Leading to Withdrawal from Study Treatment	2.6	2.9	1.6
AE of Special Interest (AESI)	6.1	7.0	4.8

No statistical analyses for this end point

Secondary: Percentage of Participants with at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye

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End point title

Percentage of Participants with at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye

End point description

This analysis of adverse events (AEs) only includes ocular AEs, which are categorized as having occurred either in the study eye or the fellow eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation.

End point type

Secondary

End point timeframe

From first dose of study drug through end of study (up to 2 years)

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	313	313	311
Units: Percentage of participants
number (not applicable)
Study Eye: Adverse Event (AE)	47.0	46.6	46.3
Study Eye: Serious AE (SAE)	3.8	4.5	2.3
Study Eye: AE Leading to Withdrawal from Treatment	1.3	1.9	0.3
Study Eye: Treatment-related AE	3.2	2.2	1.9
Study Eye: Treatment-related SAE	0.0	1.3	0.0
Study Eye: AE of Special Interest (AESI)	3.5	4.2	2.6
Study Eye: AESI, Drop in VA Score ≥30 Letters	2.6	2.2	2.3
Study Eye: AESI, Associated with Severe IOI	0.6	1.6	0.0
StudyEye:AESI,Interv Req to Avoid Perm Vision Loss	1.0	1.3	0.3
Fellow Eye: AE	40.3	42.2	46.3
Fellow Eye: SAE	2.9	3.5	2.3
Fellow Eye: AESI	2.9	2.9	2.3
Fellow Eye: AESI, Drop in VA Score ≥30 Letters	2.2	1.9	1.3
Fellow Eye: AESI, Associated with Severe IOI	0.0	0.3	0.0
FellowEye:AESI,Inter Req to Avoid Perm Vision Loss	1.0	1.3	1.0

No statistical analyses for this end point

Secondary: Percentage of Participants with at Least One Non-Ocular Adverse Event

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End point title

Percentage of Participants with at Least One Non-Ocular Adverse Event

End point description

This analysis of adverse events (AEs) only includes non-ocular (systemic) AEs. Investigators sought information on adverse events (AEs) at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. The non-ocular AE of special interest was: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.

End point type

Secondary

End point timeframe

From first dose of study drug through end of study (up to 2 years)

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Number of subjects analysed	313	313	311
Units: Percentage of participants
number (not applicable)
Adverse Event (AE)	76.7	80.2	77.8
Serious AE (SAE)	31.6	31.0	27.0
AE Leading to Withdrawal from Study Treatment	1.3	1.0	1.3
AE of Special Interest (AESI)	0.0	0.0	0.3
AESI,Elev ALT/AST +Elev Bilirubin or Clin Jaundice	0.0	0.0	0.3

No statistical analyses for this end point

Secondary: Plasma Concentration of Faricimab Over Time

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End point title

Plasma Concentration of Faricimab Over Time ^[17]

End point description

Faricimab concentration in plasma was determined using a validated immunoassay method.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 (Baseline); Weeks 4, 28, 52, 76, and 100

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only applicable to participants in Arms A and B who received treatment with faricimab and had at least one plasma sample, provided sufficient dosing information (dose and dosing time) was available.

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI
Number of subjects analysed	313	311
Units: micrograms per millilitre (μg/mL)
arithmetic mean (standard deviation)
Baseline (n = 299, 305)	0.0000 ( 0.0001 )	0.0000 ( 0.0001 )
Week 4 (n = 295, 292)	0.0211 ( 0.0337 )	0.0181 ( 0.0139 )
Week 28 (n = 261, 266)	0.0033 ( 0.0053 )	0.0089 ( 0.0145 )
Week 52 (n = 251, 255)	0.0052 ( 0.0104 )	0.0100 ( 0.0132 )
Week 76 (n = 229, 228)	0.0048 ( 0.0085 )	0.0068 ( 0.0255 )
Week 100 (n = 246, 243)	0.0052 ( 0.0087 )	0.0077 ( 0.0126 )

No statistical analyses for this end point

Secondary: Percentage of Participants who Test Positive for Treatment-Emergent Anti-Drug Antibodies Against Faricimab During the Study

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End point title

Percentage of Participants who Test Positive for Treatment-Emergent Anti-Drug Antibodies Against Faricimab During the Study ^[18]

End point description

Anti-drug antibodies (ADAs) against fariciamb were detected in plasma using a validated bridging enzyme-linked immunosorbent assay (ELISA). The percentage of participants with treatment-emergent ADA-positive samples includes post-baseline evaluable participants with at least one treatment-induced (defined as having an ADA-negative sample or missing sample at baseline and any positive post-baseline sample) or treatment-boosted (defined as having an ADA-positive sample at baseline and any positive post-baseline sample with a titer that is equal to or greater than 4-fold baseline titer) ADA-positive sample during the study treatment period.

End point type

Secondary

End point timeframe

Baseline, Weeks 4, 28, 52, 76, and 100

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only applicable to participants in Arms A and B who received treatment with faricimab and had at least one determinant post-baseline ADA assessment.

End point values	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI
Number of subjects analysed	310	311
Units: Percentage of participants
number (not applicable)
Total Treatment-Emergent ADA-Positive	12.6	10.6
Treatment-Induced ADA-Positive	12.6	10.3
Treatment-Boosted ADA-Positive	0.0	0.3

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Baseline until Week 100

Adverse event reporting additional description

Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

A: Faricimab 6 mg Q8W

Reporting group description

Reporting group title

C: Aflibercept 2 mg Q8W

Reporting group description

Reporting group title

B: Faricimab 6 mg PTI

Reporting group description

Serious adverse events	A: Faricimab 6 mg Q8W	C: Aflibercept 2 mg Q8W	B: Faricimab 6 mg PTI
Total subjects affected by serious adverse events
subjects affected / exposed	111 / 313 (35.46%)	93 / 311 (29.90%)	117 / 313 (37.38%)
number of deaths (all causes)	16	13	21
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon
subjects affected / exposed	0 / 313 (0.00%)	3 / 311 (0.96%)	2 / 313 (0.64%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Bile duct cancer
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bladder cancer
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Leukaemia
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Breast cancer
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neoplasm
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatic carcinoma
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Plasma cell myeloma
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal neoplasm
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tumour invasion
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatocellular carcinoma
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meningioma
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metastases to bone
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatic carcinoma metastatic
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Vascular disorders
Aortic stenosis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arteriosclerosis
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood pressure inadequately controlled
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Embolism
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Hypertension
subjects affected / exposed	1 / 313 (0.32%)	3 / 311 (0.96%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	1 / 1	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral artery thrombosis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Varicose vein
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Circulatory collapse
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Haematoma
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypertensive urgency
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	1 / 313 (0.32%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral artery aneurysm
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral artery stenosis
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral vascular disorder
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Coronary artery bypass
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	2 / 313 (0.64%)	2 / 311 (0.64%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	3 / 313 (0.96%)	1 / 311 (0.32%)	5 / 313 (1.60%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 3	0 / 1	0 / 5
Fatigue
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Generalised oedema
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ill-defined disorder
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Complication associated with device
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cyst
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperpyrexia
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	4 / 313 (1.28%)	3 / 311 (0.96%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 4	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Apnoea
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dyspnoea exertional
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	2 / 313 (0.64%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Pulmonary embolism
subjects affected / exposed	2 / 313 (0.64%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 313 (0.32%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Pneumothorax
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary fibrosis
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Respiratory depression
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Completed suicide
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Delusional disorder, unspecified type
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Disorientation
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Delusion
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Product issues
Device dislocation
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device malfunction
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Blood potassium increased
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood testosterone increased
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza A virus test positive
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SARS-CoV-2 test positive
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	2 / 313 (0.64%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Cataract traumatic
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Corneal abrasion
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ilium fracture
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Limb injury
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thermal burn
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	1 / 313 (0.32%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound dehiscence
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Posterior capsule rupture
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Foreign body in throat
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skull fractured base
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute left ventricular failure
subjects affected / exposed	0 / 313 (0.00%)	2 / 311 (0.64%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	5 / 313 (1.60%)	4 / 311 (1.29%)	3 / 313 (0.96%)
occurrences causally related to treatment / all	0 / 5	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 1
Angina pectoris
subjects affected / exposed	1 / 313 (0.32%)	2 / 311 (0.64%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	1 / 313 (0.32%)	1 / 311 (0.32%)	2 / 313 (0.64%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	2 / 313 (0.64%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	2 / 313 (0.64%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	3 / 313 (0.96%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 2
Cardiac failure acute
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	7 / 313 (2.24%)	5 / 311 (1.61%)	3 / 313 (0.96%)
occurrences causally related to treatment / all	0 / 12	0 / 6	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiovascular disorder
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic left ventricular failure
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	2 / 313 (0.64%)	4 / 311 (1.29%)	5 / 313 (1.60%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	2 / 313 (0.64%)	5 / 311 (1.61%)	5 / 313 (1.60%)
occurrences causally related to treatment / all	0 / 2	0 / 5	0 / 5
deaths causally related to treatment / all	0 / 1	0 / 2	0 / 1
Myocardial ischaemia
subjects affected / exposed	2 / 313 (0.64%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocarditis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pericarditis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ventricular tachyarrhythmia
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrioventricular block
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrioventricular block second degree
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiogenic shock
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure chronic
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiopulmonary failure
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Congestive cardiomyopathy
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Left ventricular failure
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Ventricular fibrillation
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ventricular tachycardia
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebral haemorrhage
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Cerebral infarction
subjects affected / exposed	3 / 313 (0.96%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	2 / 313 (0.64%)	4 / 311 (1.29%)	4 / 313 (1.28%)
occurrences causally related to treatment / all	0 / 2	2 / 4	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coma
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dizziness
subjects affected / exposed	1 / 313 (0.32%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhagic stroke
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Hypertensive encephalopathy
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoxic-ischaemic encephalopathy
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	4 / 313 (1.28%)	2 / 311 (0.64%)	2 / 313 (0.64%)
occurrences causally related to treatment / all	1 / 4	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Lumbar radiculopathy
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	2 / 313 (0.64%)	3 / 311 (0.96%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vertigo CNS origin
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebral microinfarction
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebrovascular disorder
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Lacunar infarction
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Loss of consciousness
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolic encephalopathy
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ruptured cerebral aneurysm
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Toxic encephalopathy
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 313 (0.00%)	2 / 311 (0.64%)	2 / 313 (0.64%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Anaemia of chronic disease
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood loss anaemia
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Sudden hearing loss
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vestibular disorder
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Angle closure glaucoma
subjects affected / exposed	1 / 313 (0.32%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cataract
subjects affected / exposed	4 / 313 (1.28%)	3 / 311 (0.96%)	3 / 313 (0.96%)
occurrences causally related to treatment / all	0 / 4	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic retinal oedema
subjects affected / exposed	2 / 313 (0.64%)	2 / 311 (0.64%)	2 / 313 (0.64%)
occurrences causally related to treatment / all	0 / 5	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic retinopathy
subjects affected / exposed	4 / 313 (1.28%)	2 / 311 (0.64%)	2 / 313 (0.64%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Macular fibrosis
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	2 / 313 (0.64%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Glaucoma
subjects affected / exposed	2 / 313 (0.64%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Macular oedema
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Narrow anterior chamber angle
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Retinal artery occlusion
subjects affected / exposed	0 / 313 (0.00%)	2 / 311 (0.64%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ocular hypertension
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Retinal haemorrhage
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	2 / 313 (0.64%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Retinal neovascularisation
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Retinal tear
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rhegmatogenous retinal detachment
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Uveitic glaucoma
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Uveitis
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	4 / 313 (1.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	4 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Visual acuity reduced
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vitreous haemorrhage
subjects affected / exposed	3 / 313 (0.96%)	1 / 311 (0.32%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cataract subcapsular
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ocular ischaemic syndrome
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Retinal vein occlusion
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tractional retinal detachment
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal hernia
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic gastroparesis
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Large intestine polyp
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ascites
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colitis ulcerative
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intestinal ischaemia
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Biliary dyskinesia
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholecystitis chronic
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic cirrhosis
subjects affected / exposed	1 / 313 (0.32%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic hepatitis
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Non-alcoholic steatohepatitis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Diabetic foot
subjects affected / exposed	1 / 313 (0.32%)	3 / 311 (0.96%)	3 / 313 (0.96%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Angioedema
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin ulcer
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	3 / 313 (0.96%)	4 / 311 (1.29%)	2 / 313 (0.64%)
occurrences causally related to treatment / all	0 / 3	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic kidney disease
subjects affected / exposed	2 / 313 (0.64%)	4 / 311 (1.29%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
End stage renal disease
subjects affected / exposed	3 / 313 (0.96%)	2 / 311 (0.64%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	5 / 313 (1.60%)	3 / 311 (0.96%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 6	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Renal impairment
subjects affected / exposed	1 / 313 (0.32%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	1 / 313 (0.32%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bursitis
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Muscle spasms
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neuropathic arthropathy
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neck pain
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 313 (0.00%)	2 / 311 (0.64%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteochondrosis
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthritis
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rheumatoid arthritis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess limb
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	5 / 313 (1.60%)	4 / 311 (1.29%)	10 / 313 (3.19%)
occurrences causally related to treatment / all	0 / 5	0 / 4	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 3
Cellulitis
subjects affected / exposed	4 / 313 (1.28%)	4 / 311 (1.29%)	5 / 313 (1.60%)
occurrences causally related to treatment / all	0 / 4	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis gangrenous
subjects affected / exposed	0 / 313 (0.00%)	2 / 311 (0.64%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholecystitis infective
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chorioretinitis
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Complicated appendicitis
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic foot infection
subjects affected / exposed	0 / 313 (0.00%)	3 / 311 (0.96%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic gangrene
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endophthalmitis
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	4 / 313 (1.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fungal infection
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infected bite
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Keratouveitis
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Kidney infection
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Localised infection
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	3 / 313 (0.96%)	7 / 311 (2.25%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 3	0 / 7	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	8 / 313 (2.56%)	7 / 311 (2.25%)	4 / 313 (1.28%)
occurrences causally related to treatment / all	0 / 10	0 / 7	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia escherichia
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pseudomonal sepsis
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	6 / 313 (1.92%)	7 / 311 (2.25%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 6	0 / 7	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Sepsis syndrome
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	3 / 313 (0.96%)	1 / 311 (0.32%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Viral keratouveitis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coronavirus infection
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	1 / 313 (0.32%)	3 / 311 (0.96%)	3 / 313 (0.96%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 1
Device related infection
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gangrene
subjects affected / exposed	1 / 313 (0.32%)	2 / 311 (0.64%)	4 / 313 (1.28%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Norovirus infection
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suspected COVID-19
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Septic shock
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	2 / 313 (0.64%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic complication
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	1 / 313 (0.32%)	1 / 311 (0.32%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic metabolic decompensation
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	3 / 313 (0.96%)	1 / 311 (0.32%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 313 (0.00%)	1 / 311 (0.32%)	4 / 313 (1.28%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	2 / 313 (0.64%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lactic acidosis
subjects affected / exposed	1 / 313 (0.32%)	0 / 311 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperosmolar state
subjects affected / exposed	0 / 313 (0.00%)	0 / 311 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	A: Faricimab 6 mg Q8W	C: Aflibercept 2 mg Q8W	B: Faricimab 6 mg PTI
Total subjects affected by non serious adverse events
subjects affected / exposed	161 / 313 (51.44%)	163 / 311 (52.41%)	163 / 313 (52.08%)
Investigations
Intraocular pressure increased
subjects affected / exposed	17 / 313 (5.43%)	11 / 311 (3.54%)	13 / 313 (4.15%)
occurrences all number	28	13	25
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	16 / 313 (5.11%)	9 / 311 (2.89%)	19 / 313 (6.07%)
occurrences all number	16	9	20
Vascular disorders
Hypertension
subjects affected / exposed	22 / 313 (7.03%)	36 / 311 (11.58%)	32 / 313 (10.22%)
occurrences all number	27	38	34
Eye disorders
Conjunctival haemorrhage
subjects affected / exposed	25 / 313 (7.99%)	24 / 311 (7.72%)	33 / 313 (10.54%)
occurrences all number	35	32	41
Cataract
subjects affected / exposed	58 / 313 (18.53%)	55 / 311 (17.68%)	47 / 313 (15.02%)
occurrences all number	84	82	65
Vitreous detachment
subjects affected / exposed	20 / 313 (6.39%)	13 / 311 (4.18%)	23 / 313 (7.35%)
occurrences all number	25	16	28
Diabetic retinal oedema
subjects affected / exposed	20 / 313 (6.39%)	33 / 311 (10.61%)	29 / 313 (9.27%)
occurrences all number	27	40	37
Vitreous floaters
subjects affected / exposed	17 / 313 (5.43%)	10 / 311 (3.22%)	11 / 313 (3.51%)
occurrences all number	25	13	13
Infections and infestations
Nasopharyngitis
subjects affected / exposed	27 / 313 (8.63%)	30 / 311 (9.65%)	18 / 313 (5.75%)
occurrences all number	31	39	23
Urinary tract infection
subjects affected / exposed	14 / 313 (4.47%)	19 / 311 (6.11%)	15 / 313 (4.79%)
occurrences all number	23	22	17

More information

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Were there any global substantial amendments to the protocol? Yes

23 Aug 2018

- Protocol GR40349 has been amended to include additional prohibited medications (Section 4.4.2) and more detailed examples of contraceptive methods for females of childbearing potential (Section 4.1.1.1) to enhance patient safety and to comply with health authority requests, enabling this protocol to be conducted globally.

20 Jun 2019

- The China enrollment plan and extension has been removed from the study since this study is not being conducted in China. A Japan enrollment plan and extension has been established and added to the study since patient recruitment is expected to take longer in Japan.; - The study eye ocular exclusion criterion has been modified to include vitreomacular traction, which will be evaluated by the CRC for eligibility. - The concurrent ocular conditions exclusion criterion has been modified to include retinal embolus.; - A section for risks associated with aflibercept has been added.; - Study treatment interruption due to active or suspected infection has been expanded to include "suspected ocular or periocular infections".; - Criteria for study treatment interruption due to IOI have been updated such that study treatment may be resumed subsequently as determined by the investigator.; - Reporting of medication errors and associated AEs in Section 5.4.4 was updated and moved to Section 5.3.5.12. The medication errors themselves will no longer be reported expeditiously (within 24 hours). However, if they cause a SAE or AESI, these will continue to be reported in an expedited manner.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

All secondary outcome measures were unpowered for statistical analysis, and the results should be interpreted with caution.

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Clinical trials

Clinical Trial Results: A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Patients with Diabetic Macular Edema (YOSEMITE)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

Primary: Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

Secondary: Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale at Week 52, ITT and Treatment-Naive Populations

Secondary: Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale at Week 52, ITT and Treatment-Naive Populations

Secondary: Change from Baseline in BCVA in the Study Eye Over Time, ITT Population

Secondary: Change from Baseline in BCVA in the Study Eye Over Time, ITT Population

Secondary: Change from Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population

Secondary: Change from Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population

Secondary: Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population

Secondary: Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population

Secondary: Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population

Secondary: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population

Secondary: Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA from Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population

Secondary: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants Gaining ≥15 Letters in BCVA from Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants with BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants with a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants with a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

Secondary: Percentage of Participants with a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

Secondary: Percentage of Participants with a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

Clinical Trial Results:
A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Patients with Diabetic Macular Edema (YOSEMITE)