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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 (RHINE)

Summary
EudraCT number	2017-005105-12
Trial protocol	PT HU DE CZ GB DK ES IT
Global end of trial date	27 Aug 2021

Results information
Results version number	v1(current)
This version publication date	02 Sep 2022
First version publication date	02 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

GR40398

ISRCTN number

US NCT number

NCT03622593

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche, Ltd.

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland,

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

27 Aug 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

19 Oct 2020

Global end of trial reached?

Yes

Global end of trial date

27 Aug 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

09 Oct 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 94

Country: Number of subjects enrolled

Australia: 27

Country: Number of subjects enrolled

Brazil: 52

Country: Number of subjects enrolled

Canada: 25

Country: Number of subjects enrolled

China: 1

Country: Number of subjects enrolled

Czechia: 67

Country: Number of subjects enrolled

Denmark: 3

Country: Number of subjects enrolled

France: 7

Country: Number of subjects enrolled

Germany: 8

Country: Number of subjects enrolled

Hong Kong: 11

Country: Number of subjects enrolled

Hungary: 30

Country: Number of subjects enrolled

Italy: 11

Country: Number of subjects enrolled

Korea, Republic of: 29

Country: Number of subjects enrolled

Poland: 93

Country: Number of subjects enrolled

Portugal: 21

Country: Number of subjects enrolled

Russian Federation: 23

Country: Number of subjects enrolled

Singapore: 8

Country: Number of subjects enrolled

Spain: 31

Country: Number of subjects enrolled

Switzerland: 1

Country: Number of subjects enrolled

Taiwan: 21

Country: Number of subjects enrolled

Thailand: 14

Country: Number of subjects enrolled

Turkey: 11

Country: Number of subjects enrolled

United Kingdom: 58

Country: Number of subjects enrolled

United States: 305

Worldwide total number of subjects

951

EEA total number of subjects

271

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)

542

From 65 to 84 years

406

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 1715 patients were screened, and 764 patients failed screening due to not meeting the inclusion criteria. A total of 951 patients with DME were randomized 1:1:1 using a stratified permuted-block randomization scheme into the study: 317 to Arm A: Faricimab 6 mg Q8W, 319 to Arm B: Faricimab 6 mg PTI, and 315 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	317	319	315
Received at Least One Dose of Study Drug	317	319	314
Completed up to Week 56	298	312	299
Completed	275	288	267
Not completed	42	31	48
Consent withdrawn by subject	11	9	13
Physician decision	2	1	6
Adverse event, non-fatal	4	5	6
Death	12	9	10
Not Specified	2	2	3
Pregnancy	-	-	1
Lost to follow-up	11	5	8
Protocol deviation	-	-	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	317	319	315	951
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)	176	183	183	542
From 65-84 years	140	135	131	406
85 years and over	1	1	1	3
Age Continuous
Units: Years
arithmetic mean (standard deviation)	62.5 ( 10.1 )	61.6 ( 10.1 )	62.3 ( 10.1 )	-
Sex: Female, Male
Units: Participants
Female	123	120	129	372
Male	194	199	186	579
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	254	255	248	757
Previously Treated	63	64	67	194
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	1	1
Asian	34	36	32	102
Native Hawaiian or Other Pacific Islander	2	0	0	2
Black or African American	18	23	24	65
White	250	249	253	752
More than one race	2	1	0	3
Unknown or Not Reported	11	10	5	26
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	56	78	67	201
Not Hispanic or Latino	252	232	240	724
Unknown or Not Reported	9	9	8	26
Region of Enrollment
Units: Subjects
United States and Canada	110	111	109	330
Asia	29	29	26	84
Rest of the World	178	179	180	537
Number of Participants by the Eye Chosen as the Study Eye (Left or Right)
Units: Subjects
Left Eye	156	168	146	470
Right Eye	161	151	169	481
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	14	11	9	34
39 to 63 Letters	128	132	132	392
≥64 Letters	174	174	174	522
Missing/Invalid BCVA	1	2	0	3
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 the central reading center.
Units: Subjects
1 - Diabetic Retinopathy (DR) Absent	2	4	1	7
2 - DR Questionable / Microaneurysms Only	3	10	6	19
3 - Mild Non-Proliferative DR (NPDR)	90	92	94	276
4 - Moderate NPDR	88	72	79	239
5 - Moderately Severe NPDR	59	63	54	176
6 - Severe NPDR	50	36	51	137
7 - Mild Proliferative Diabetic Retinopathy (PDR)	12	26	11	49
8 - Moderate PDR	6	10	6	22
9 - High Risk PDR (DRS Level 71)	2	1	3	6
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	2	5	5	12
Missing	3	0	5	8
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)	61.9 ( 10.1 )	62.5 ( 9.3 )	62.1 ( 9.4 )	-
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 the central reading center.
Units: microns
arithmetic mean (standard deviation)	466.2 ( 119.4 )	471.3 ( 127.0 )	477.3 ( 129.4 )	-

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	254	255	248
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)	62.5 ( 9.9 )	61.3 ( 10.3 )	62.5 ( 10.0 )
Sex: Female, Male
Units: Participants
Female	100	94	97
Male	154	161	151
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	0	0	0
Asian	26	29	25
Native Hawaiian or Other Pacific Islander	2	0	0
Black or African American	16	20	17
White	197	197	201
More than one race	2	1	0
Unknown or Not Reported	11	8	5
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	42	57	54
Not Hispanic or Latino	204	190	188
Unknown or Not Reported	8	8	6
Region of Enrollment
Units: Subjects
United States and Canada	87	88	84
Asia	23	24	21
Rest of the World	144	143	143
Number of Participants by the Eye Chosen as the Study Eye (Left or Right)
Units: Subjects
Left Eye	128	136	117
Right Eye	126	119	131
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	8	5
39 to 63 Letters	100	103	100
≥64 Letters	143	142	143
Missing/Invalid BCVA	1	2	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 the central reading center.
Units: Subjects
1 - Diabetic Retinopathy (DR) Absent	2	3	1
2 - DR Questionable / Microaneurysms Only	1	8	6
3 - Mild Non-Proliferative DR (NPDR)	63	66	71
4 - Moderate NPDR	74	59	56
5 - Moderately Severe NPDR	48	56	43
6 - Severe NPDR	44	32	47
7 - Mild Proliferative Diabetic Retinopathy (PDR)	11	17	7
8 - Moderate PDR	5	9	5
9 - High Risk PDR (DRS Level 71)	2	1	3
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	1	4	4
Missing	3	0	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)	62.1 ( 10.1 )	62.8 ( 9.3 )	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 the central reading center.
Units: microns
arithmetic mean (standard deviation)	464.6 ( 117.9 )	473.0 ( 130.5 )	474.3 ( 129.5 )

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	317	319	315	254	255	248
Units: ETDRS Letters
arithmetic mean (confidence interval 97.5%)	11.8 (10.6 to 13.0)	10.8 (9.6 to 11.9)	10.3 (9.1 to 11.4)	11.7 (10.4 to 13.0)	11.2 (9.9 to 12.4)	10.5 (9.2 to 11.9)

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

632

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

Method

Parameter type

Adjusted mean difference

Point estimate

1.5

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.1

upper limit

3.2

Variability estimate

Standard error of the mean

Dispersion value

0.73

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

634

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Parameter type

Adjusted mean difference

Point estimate

0.5

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1.1

upper limit

2.1

Variability estimate

Standard error of the mean

Dispersion value

0.73

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

502

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1718 ^[3]

Method

Mixed Model for Repeated Measures

Parameter type

Adjusted mean difference

Point estimate

1.1

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.7

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.83

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

503

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4602 ^[4]

Method

Mixed Model for Repeated Measures

Parameter type

Adjusted mean difference

Point estimate

0.6

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1.2

upper limit

2.4

Variability estimate

Standard error of the mean

Dispersion value

0.82

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

632

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0361 ^[5]

Method

Mixed Model for Repeated Measures

Parameter type

Adjusted mean difference

Point estimate

1.5

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.1

upper limit

3.2

Variability estimate

Standard error of the mean

Dispersion value

0.73

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

634

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.493 ^[6]

Method

Mixed Model for Repeated Measures

Parameter type

Adjusted mean difference

Point estimate

0.5

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1.1

upper limit

2.1

Variability estimate

Standard error of the mean

Dispersion value

0.73

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

Secondary: Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity (DRS) Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) 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 (DRS) Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) 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	231	251	238	179	198	184
Units: Percentage of participants
number (confidence interval 97.5%)	44.2 (37.1 to 51.4)	43.7 (36.8 to 50.7)	46.8 (39.8 to 53.8)	46.9 (38.7 to 55.1)	45.7 (37.8 to 53.7)	52.3 (44.2 to 60.4)

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

Statistical analysis description

This analysis 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

469

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-2.6

Confidence interval

level

97.5%

sides

2-sided

lower limit

-12.6

upper limit

7.4

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 Q8W and the active comparator (aflibercept Q8W) arms was greater than –10%, then faricimab Q8W was considered non-inferior to aflibercept.

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

Statistical analysis description

This analysis 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

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-3.5

Confidence interval

level

97.5%

sides

2-sided

lower limit

-13.4

upper limit

6.3

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 PTI and the active comparator (aflibercept Q8W) arms was greater than –10%, then faricimab PTI was considered non-inferior to aflibercept.

Superiority: Arm A vs. Arm C, TN

Statistical analysis description

This analysis 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

363

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3009 ^[9]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-5.4

Confidence interval

level

97.5%

sides

2-sided

lower limit

-16.9

upper limit

6.1

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

Superiority: Arm B vs. Arm C, TN

Statistical analysis description

This analysis 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

382

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1735 ^[10]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-6.9

Confidence interval

level

97.5%

sides

2-sided

lower limit

-18.3

upper limit

4.4

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

Superiority: Arm A vs. Arm C, ITT

Statistical analysis description

This analysis 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

469

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5757 ^[11]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-2.6

Confidence interval

level

97.5%

sides

2-sided

lower limit

-12.6

upper limit

7.4

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

Superiority: Arm B vs. Arm C, ITT

Statistical analysis description

This analysis 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

489

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4293 ^[12]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in CMH Weighted Percentage

Point estimate

-3.5

Confidence interval

level

97.5%

sides

2-sided

lower limit

-13.4

upper limit

6.3

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	317	319	315
Units: ETDRS Letters
arithmetic mean (confidence interval 95%)
Week 4	6.1 (5.4 to 6.8)	6.6 (5.8 to 7.3)	6.4 (5.7 to 7.1)
Week 8	7.8 (7.0 to 8.5)	8.1 (7.4 to 8.9)	7.5 (6.8 to 8.3)
Week 12	8.7 (7.8 to 9.5)	9.1 (8.2 to 9.9)	8.5 (7.7 to 9.4)
Week 16	9.9 (9.0 to 10.7)	9.8 (9.0 to 10.7)	8.8 (7.9 to 9.6)
Week 20	10.1 (9.2 to 10.9)	9.5 (8.6 to 10.4)	8.8 (8.0 to 9.7)
Week 24	10.6 (9.7 to 11.5)	9.9 (9.0 to 10.8)	9.3 (8.4 to 10.2)
Week 28	10.7 (9.7 to 11.6)	10.5 (9.6 to 11.4)	9.6 (8.7 to 10.5)
Week 32	11.3 (10.3 to 12.3)	10.2 (9.2 to 11.1)	9.4 (8.5 to 10.4)
Week 36	11.0 (10.1 to 12.0)	10.6 (9.6 to 11.6)	10.4 (9.5 to 11.4)
Week 40	11.4 (10.3 to 12.5)	10.7 (9.6 to 11.7)	10.3 (9.2 to 11.3)
Week 44	11.7 (10.7 to 12.7)	10.9 (9.9 to 11.9)	10.5 (9.5 to 11.5)
Week 48	11.8 (10.7 to 12.9)	10.6 (9.5 to 11.7)	10.1 (9.0 to 11.1)
Week 52	11.6 (10.5 to 12.6)	10.7 (9.6 to 11.7)	10.4 (9.3 to 11.4)
Week 56	11.6 (10.4 to 12.8)	10.6 (9.5 to 11.8)	9.9 (8.7 to 11.1)
Week 60	11.4 (10.2 to 12.6)	10.1 (8.9 to 11.3)	10.1 (8.9 to 11.3)
Week 64	11.6 (10.4 to 12.7)	10.3 (9.2 to 11.5)	9.4 (8.2 to 10.6)
Week 68	11.2 (10.0 to 12.3)	10.1 (9.0 to 11.3)	10.0 (8.8 to 11.1)
Week 72	11.2 (9.9 to 12.4)	9.9 (8.8 to 11.1)	9.4 (8.2 to 10.6)
Week 76	10.6 (9.3 to 11.9)	9.4 (8.1 to 10.7)	9.5 (8.2 to 10.8)
Week 80	10.6 (9.2 to 12.0)	9.5 (8.1 to 10.9)	9.1 (7.7 to 10.5)
Week 84	9.8 (8.4 to 11.2)	10.3 (9.0 to 11.7)	9.6 (8.2 to 11.0)
Week 88	9.8 (8.4 to 11.3)	10.0 (8.6 to 11.4)	9.2 (7.7 to 10.6)
Week 92	10.8 (9.3 to 12.2)	10.2 (8.8 to 11.7)	9.3 (7.9 to 10.8)
Week 96	11.3 (9.8 to 12.8)	10.5 (9.1 to 12.0)	9.0 (7.5 to 10.5)
Week 100	10.7 (9.1 to 12.3)	9.5 (7.9 to 11.0)	9.8 (8.2 to 11.4)

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	254	254 ^[13]	248
Units: ETDRS Letters
arithmetic mean (confidence interval 95%)
Week 4	6.0 (5.2 to 6.9)	6.7 (5.8 to 7.5)	6.3 (5.4 to 7.1)
Week 8	7.5 (6.6 to 8.4)	8.2 (7.3 to 9.1)	7.3 (6.4 to 8.2)
Week 12	8.7 (7.8 to 9.6)	9.2 (8.3 to 10.1)	8.5 (7.6 to 9.5)
Week 16	9.7 (8.8 to 10.7)	10.0 (9.1 to 10.9)	8.7 (7.8 to 9.6)
Week 20	10.0 (9.1 to 11.0)	9.8 (8.8 to 10.7)	9.0 (8.1 to 10.0)
Week 24	10.6 (9.6 to 11.6)	10.2 (9.2 to 11.2)	9.4 (8.4 to 10.4)
Week 28	10.8 (9.8 to 11.8)	10.8 (9.8 to 11.8)	9.9 (8.9 to 10.9)
Week 32	11.2 (10.1 to 12.3)	10.3 (9.2 to 11.4)	9.9 (8.8 to 11.0)
Week 36	10.8 (9.7 to 11.9)	10.9 (9.8 to 12.0)	10.5 (9.3 to 11.6)
Week 40	11.3 (10.2 to 12.5)	11.2 (10.0 to 12.3)	10.6 (9.5 to 11.8)
Week 44	11.5 (10.4 to 12.7)	11.2 (10.1 to 12.3)	11.1 (9.9 to 12.2)
Week 48	11.4 (10.2 to 12.7)	10.9 (9.7 to 12.1)	10.5 (9.3 to 11.7)
Week 52	11.7 (10.5 to 12.8)	11.1 (9.9 to 12.2)	10.7 (9.5 to 11.9)
Week 56	11.4 (10.0 to 12.8)	11.0 (9.6 to 12.3)	10.0 (8.6 to 11.4)
Week 60	11.4 (10.0 to 12.7)	10.5 (9.2 to 11.8)	10.1 (8.8 to 11.5)
Week 64	11.6 (10.2 to 12.9)	10.5 (9.2 to 11.8)	9.5 (8.2 to 10.8)
Week 68	11.2 (9.9 to 12.5)	10.3 (9.0 to 11.6)	10.0 (8.7 to 11.3)
Week 72	11.1 (9.7 to 12.5)	10.1 (8.8 to 11.5)	9.6 (8.2 to 10.9)
Week 76	10.6 (9.0 to 12.1)	9.7 (8.2 to 11.2)	9.5 (8.0 to 11.1)
Week 80	10.9 (9.4 to 12.5)	10.0 (8.5 to 11.5)	9.3 (7.8 to 10.9)
Week 84	9.9 (8.4 to 11.5)	10.8 (9.3 to 12.3)	9.6 (8.0 to 11.1)
Week 88	9.6 (7.9 to 11.2)	10.2 (8.6 to 11.8)	9.4 (7.8 to 11.1)
Week 92	10.4 (8.8 to 12.1)	10.6 (9.0 to 12.2)	9.6 (7.9 to 11.2)
Week 96	10.6 (8.9 to 12.3)	10.9 (9.2 to 12.5)	9.0 (7.3 to 10.7)
Week 100	10.4 (8.5 to 12.2)	10.0 (8.2 to 11.7)	9.8 (7.9 to 11.6)

Notes
[13] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	268	293	279
Units: Percentage of participants
number (confidence interval 95%)
Gaining ≥15 Letters	33.8 (28.4 to 39.2)	28.5 (23.6 to 33.3)	30.3 (25.0 to 35.5)
Gaining ≥10 Letters	59.3 (53.6 to 64.9)	53.0 (47.5 to 58.5)	53.9 (48.3 to 59.5)
Gaining ≥5 Letters	81.8 (77.3 to 86.4)	77.4 (72.7 to 82.1)	78.0 (73.3 to 82.7)
Gaining ≥0 Letters	92.1 (89.0 to 95.3)	91.1 (87.8 to 94.3)	91.4 (88.2 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

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

11.1

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

572

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

-9.1

upper limit

5.2

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

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

13.4

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

572

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

-8.9

upper limit

6.8

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

3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

10.3

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 v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

572

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

-7.3

upper limit

5.9

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 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

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8

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 v C: Aflibercept 2 mg Q8W

Number of subjects included in analysis

572

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

-4.9

upper limit

4.2

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 307,306,309)	13.4 (9.9 to 17.0)	10.8 (7.5 to 14.2)	10.6 (7.3 to 14.0)
Week 8 (n = 305,311,309)	15.2 (11.2 to 19.1)	16.7 (12.7 to 20.8)	15.4 (11.5 to 19.4)
Week 12 (n = 305,303,302)	20.7 (16.3 to 25.1)	22.1 (17.6 to 26.5)	19.3 (15.0 to 23.6)
Week 16 (n = 300,304,296)	24.4 (19.7 to 29.1)	24.3 (19.7 to 28.8)	23.1 (18.5 to 27.7)
Week 20 (n = 294,302,295)	26.7 (21.8 to 31.6)	21.3 (16.8 to 25.7)	22.8 (18.3 to 27.4)
Week 24 (n = 293,306,297)	29.8 (24.7 to 34.9)	24.0 (19.3 to 28.6)	24.6 (19.8 to 29.3)
Week 28 (n = 284,295,287)	30.1 (25.0 to 35.3)	26.7 (21.9 to 31.5)	25.7 (20.7 to 30.6)
Week 32 (n = 277,284,280)	35.9 (30.6 to 41.3)	27.3 (22.2 to 32.3)	23.9 (19.1 to 28.7)
Week 36 (n = 275,281,275)	33.8 (28.5 to 39.1)	32.1 (27.0 to 37.2)	28.5 (23.5 to 33.5)
Week 40 (n = 275,286,274)	37.8 (32.3 to 43.3)	30.5 (25.4 to 35.6)	29.1 (24.0 to 34.2)
Week 44 (n = 269,286,272)	37.1 (31.6 to 42.5)	30.1 (25.0 to 32.5)	33.4 (28.0 to 38.7)
Week 48 (n = 255,286,278)	33.0 (27.5 to 38.6)	29.4 (24.4 to 34.3)	29.3 (24.1 to 34.4)
Week 52 (n = 267,281,271)	35.0 (29.6 to 40.4)	31.0 (25.9 to 36.2)	33.1 (27.7 to 38.5)
Week 56 (n = 267,283,261)	38.8 (33.2 to 44.3)	29.5 (24.5 to 34.6)	36.4 (30.7 to 42.0)
Week 60 (n = 261,277,255)	38.0 (32.3 to 43.7)	30.3 (25.2 to 35.5)	36.6 (30.9 to 42.3)
Week 64 (n = 258,290,259)	40.3 (34.7 to 45.9)	29.6 (24.5 to 34.8)	31.9 (26.5 to 37.3)
Week 68 (n = 254,272,255)	36.9 (31.3 to 42.5)	31.1 (25.8 to 36.5)	35.4 (29.8 to 41.0)
Week 72 (n = 245,261,250)	36.8 (31.0 to 42.6)	30.5 (25.1 to 35.8)	32.5 (26.9 to 38.0)
Week 76 (n = 257,273,251)	37.1 (31.5 to 42.7)	31.2 (25.9 to 36.6)	35.1 (29.4 to 40.8)
Week 80 (n = 247,269,250)	39.6 (33.8 to 45.5)	30.1 (24.8 to 35.3)	35.3 (29.6 to 41.1)
Week 84 (n = 253,265,255)	38.5 (32.9 to 44.2)	30.6 (25.2 to 36.0)	38.1 (32.4 to 43.9)
Week 88 (n = 254,267,247)	40.4 (34.7 to 46.1)	29.6 (24.3 to 35.0)	38.5 (32.6 to 44.3)
Week 92 (n = 249,269,242)	42.3 (36.4 to 48.1)	34.6 (29.2 to 40.0)	42.1 (36.0 to 48.2)
Week 96 (n = 244,267,241)	44.2 (38.1 to 50.2)	34.4 (29.0 to 39.7)	36.0 (30.1 to 41.8)
Week 100 (n = 251,271,237)	43.1 (37.1 to 49.1)	31.2 (25.9 to 36.5)	40.8 (34.8 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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 307,306,309)	29.1 (24.2 to 34.0)	26.9 (22.1 to 31.8)	28.7 (23.8 to 33.6)
Week 8 (n = 305,311,309)	39.7 (34.4 to 45.1)	41.4 (36.0 to 46.9)	34.8 (29.6 to 40.0)
Week 12 (n = 305,303,302)	44.8 (39.3 to 50.2)	46.9 (41.4 to 52.4)	43.2 (37.7 to 48.8)
Week 16 (n = 300,304,296)	52.5 (46.9 to 58.0)	51.3 (45.9 to 56.7)	41.8 (36.3 to 47.3)
Week 20 (n = 294,302,295)	54.0 (48.6 to 59.5)	50.0 (44.5 to 55.6)	45.5 (40.0 to 51.0)
Week 24 (n = 293,306,297)	57.0 (51.5 to 62.5)	52.8 (47.4 to 58.3)	48.4 (42.9 to 53.9)
Week 28 (n = 284,295,287)	58.3 (52.7 to 63.9)	51.3 (45.8 to 56.8)	51.7 (46.1 to 57.3)
Week 32 (n = 277,284,280)	60.1 (54.4 to 65.8)	50.9 (45.2 to 56.6)	52.5 (46.8 to 58.1)
Week 36 (n = 275,281,275)	58.6 (52.9 to 64.2)	57.3 (51.7 to 62.9)	58.7 (53.0 to 64.3)
Week 40 (n = 275,286,274)	61.8 (56.2 to 67.4)	56.0 (50.5 to 61.6)	55.8 (50.2 to 61.4)
Week 44 (n = 269,286,272)	62.0 (56.3 to 67.6)	55.9 (50.3 to 61.5)	57.2 (51.6 to 62.8)
Week 48 (n = 255,286,278)	58.0 (52.1 to 63.9)	56.7 (51.1 to 62.2)	56.3 (50.7 to 61.9)
Week 52 (n = 267,281,271)	61.1 (55.4 to 66.8)	58.7 (53.1 to 64.3)	57.1 (51.4 to 62.8)
Week 56 (n = 267,283,261)	60.7 (55.1 to 66.4)	55.9 (50.3 to 61.5)	56.2 (50.4 to 62.0)
Week 60 (n = 261,277,255)	58.5 (52.7 to 64.4)	53.7 (48.1 to 59.4)	57.0 (51.0 to 63.0)
Week 64 (n = 258,290,259)	59.7 (53.8 to 65.5)	54.5 (48.9 to 60.1)	51.5 (45.6 to 57.4)
Week 68 (n = 254,272,255)	60.2 (54.5 to 66.0)	54.1 (48.3 to 60.0)	60.7 (54.8 to 66.5)
Week 72 (n = 245,261,250)	59.2 (53.1 to 62.5)	55.6 (49.8 to 61.4)	56.6 (50.7 to 62.5)
Week 76 (n = 257,273,251)	58.7 (52.9 to 64.6)	52.5 (46.7 to 58.3)	57.0 (51.0 to 62.9)
Week 80 (n = 247,269,250)	59.6 (53.6 to 65.6)	55.0 (49.2 to 60.7)	56.5 (50.4 to 62.5)
Week 84 (n = 253,265,255)	56.2 (50.3 to 62.1)	53.3 (47.5 to 59.1)	55.8 (49.8 to 61.8)
Week 88 (n = 254,267,247)	58.3 (52.4 to 64.1)	53.5 (47.6 to 59.5)	57.0 (51.0 to 63.0)
Week 92 (n = 249,269,242)	59.5 (53.6 to 65.4)	55.0 (49.2 to 60.8)	58.5 (52.5 to 64.5)
Week 96 (n = 244,267,241)	65.4 (59.5 to 71.2)	58.0 (52.1 to 63.8)	58.8 (52.6 to 64.9)
Week 100 (n = 251,271,237)	63.7 (58.0 to 69.3)	54.0 (48.2 to 59.9)	65.3 (59.5 to 71.2)

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 307,306,309)	57.8 (52.3 to 63.2)	61.8 (56.4 to 67.2)	59.2 (53.7 to 64.6)
Week 8 (n = 305,311,309)	67.0 (61.9 to 72.2)	68.8 (63.7 to 73.9)	66.0 (60.7 to 71.2)
Week 12 (n = 305,303,302)	70.9 (65.9 to 76.0)	74.3 (69.4 to 79.2)	72.5 (67.4 to 77.5)
Week 16 (n = 300,304,296)	75.4 (70.6 to 80.2)	74.6 (69.9 to 79.4)	69.6 (64.4 to 74.8)
Week 20 (n = 294,302,295)	76.0 (71.2 to 80.8)	79.5 (75.1 to 84.0)	71.4 (66.3 to 76.6)
Week 24 (n = 293,306,297)	78.3 (73.7 to 83.0)	76.3 (71.6 to 80.9)	72.2 (67.2 to 77.2)
Week 28 (n = 284,295,287)	76.8 (72.0 to 81.7)	79.4 (74.8 to 83.9)	77.2 (72.4 to 81.9)
Week 32 (n = 277,284,280)	80.0 (75.4 to 84.6)	78.3 (73.6 to 83.0)	75.9 (70.9 to 80.8)
Week 36 (n = 275,281,275)	79.0 (74.2 to 83.8)	80.0 (75.4 to 84.6)	78.4 (73.7 to 83.2)
Week 40 (n = 275,286,274)	79.5 (74.8 to 84.2)	78.0 (73.2 to 82.7)	79.8 (75.1 to 84.5)
Week 44 (n = 269,286,272)	84.0 (79.7 to 88.3)	77.5 (72.8 to 82.3)	81.9 (77.5 to 86.3)
Week 48 (n = 255,286,278)	81.3 (76.7 to 86.0)	81.5 (77.1 to 85.9)	77.2 (72.4 to 82.0)
Week 52 (n = 267,281,271)	81.7 (77.1 to 86.3)	78.2 (73.5 to 83.0)	77.1 (72.2 to 82.0)
Week 56 (n = 267,283,261)	78.6 (73.8 to 83.4)	79.2 (74.5 to 83.8)	80.3 (75.7 to 84.9)
Week 60 (n = 261,277,255)	75.7 (70.5 to 80.8)	75.9 (71.0 to 80.9)	80.3 (75.4 to 85.1)
Week 64 (n = 258,290,259)	77.6 (72.6 to 82.6)	77.3 (72.5 to 82.0)	72.5 (67.2 to 77.8)
Week 68 (n = 254,272,255)	77.0 (72.0 to 82.1)	76.0 (70.9 to 81.0)	78.5 (73.5 to 83.4)
Week 72 (n = 245,261,250)	79.5 (74.5 to 84.4)	76.7 (71.6 to 81.7)	76.1 (70.8 to 81.3)
Week 76 (n = 257,273,251)	75.6 (70.5 to 80.8)	73.8 (68.7 to 78.9)	72.6 (67.1 to 78.0)
Week 80 (n = 247,269,250)	74.9 (69.7 to 80.2)	75.4 (70.3 to 80.5)	77.4 (72.2 to 82.5)
Week 84 (n = 253,265,255)	73.1 (67.7 to 78.4)	79.9 (75.2 to 84.7)	75.2 (70.0 to 80.3)
Week 88 (n = 254,267,247)	74.2 (69.0 to 79.5)	74.3 (69.2 to 79.5)	77.5 (72.4 to 82.6)
Week 92 (n = 249,269,242)	76.5 (71.3 to 81.7)	76.6 (71.6 to 81.6)	77.4 (72.2 to 82.6)
Week 96 (n = 244,267,241)	80.9 (76.1 to 85.7)	76.2 (71.2 to 81.2)	76.0 (70.7 to 81.3)
Week 100 (n = 251,271,237)	80.0 (75.1 to 84.8)	75.3 (70.3 to 80.4)	81.3 (76.3 to 86.2)

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 307,306,309)	85.1 (81.2 to 89.0)	89.2 (85.8 to 92.7)	89.3 (85.9 to 92.8)
Week 8 (n = 305,311,309)	90.2 (86.9 to 93.5)	91.3 (88.2 to 94.4)	90.3 (87.0 to 93.6)
Week 12 (n = 305,303,302)	90.8 (87.6 to 94.0)	92.7 (89.8 to 95.6)	90.4 (87.1 to 93.7)
Week 16 (n = 300,304,296)	92.4 (89.4 to 95.3)	91.1 (88.0 to 94.3)	90.9 (87.7 to 94.1)
Week 20 (n = 294,302,295)	92.2 (89.1 to 95.3)	91.7 (88.6 to 94.8)	93.9 (91.2 to 96.6)
Week 24 (n = 293,306,297)	91.5 (88.3 to 94.7)	91.5 (88.5 to 94.6)	91.5 (88.4 to 94.7)
Week 28 (n = 284,295,287)	92.2 (89.1 to 95.4)	94.3 (91.7 to 96.8)	94.0 (91.4 to 96.7)
Week 32 (n = 277,284,280)	91.4 (88.2 to 94.7)	90.9 (87.6 to 94.2)	92.8 (89.8 to 95.8)
Week 36 (n = 275,281,275)	92.4 (89.3 to 95.5)	90.5 (87.1 to 93.8)	95.0 (92.5 to 97.5)
Week 40 (n = 275,286,274)	92.0 (88.8 to 95.2)	92.3 (89.3 to 95.4)	93.1 (90.1 to 96.0)
Week 44 (n = 269,286,272)	91.8 (88.5 to 95.1)	91.2 (88.0 to 94.5)	92.6 (89.6 to 95.6)
Week 48 (n = 255,286,278)	93.7 (90.7 to 96.7)	91.0 (87.7 to 94.3)	91.4 (88.2 to 94.6)
Week 52 (n = 267,281,271)	93.6 (90.7 to 96.5)	90.4 (86.9 to 93.8)	91.9 (88.7 to 95.1)
Week 56 (n = 267,283,261)	92.7 (89.6 to 95.7)	91.5 (88.3 to 94.7)	90.9 (87.5 to 94.3)
Week 60 (n = 261,277,255)	89.3 (85.6 to 93.0)	88.5 (84.9 to 92.2)	92.6 (89.5 to 95.8)
Week 64 (n = 258,290,259)	91.3 (87.9 to 94.6)	89.7 (86.2 to 93.2)	87.4 (83.4 to 91.4)
Week 68 (n = 254,272,255)	89.4 (85.6 to 93.2)	90.5 (87.0 to 94.0)	91.3 (87.8 to 94.7)
Week 72 (n = 245,261,250)	89.1 (85.2 to 93.0)	90.4 (86.8 to 94.0)	88.4 (84.5 to 92.3)
Week 76 (n = 257,273,251)	89.6 (86.0 to 93.3)	86.3 (82.3 to 90.3)	90.3 (86.7 to 94.0)
Week 80 (n = 247,269,250)	86.6 (82.5 to 90.8)	88.5 (84.7 to 92.3)	88.6 (84.6 to 92.5)
Week 84 (n = 253,265,255)	87.1 (83.0 to 91.2)	90.2 (86.7 to 93.7)	87.9 (83.9 to 91.9)
Week 88 (n = 254,267,247)	84.4 (80.0 to 88.9)	89.5 (85.9 to 93.1)	88.1 (84.1 to 92.0)
Week 92 (n = 249,269,242)	86.7 (82.5 to 90.9)	86.7 (82.6 to 90.7)	87.1 (82.9 to 91.3)
Week 96 (n = 244,267,241)	86.5 (82.3 to 90.7)	87.0 (83.0 to 91.0)	89.1 (85.2 to 93.1)
Week 100 (n = 251,271,237)	86.1 (81.8 to 90.3)	87.5 (83.7 to 91.4)	91.1 (87.5 to 94.7)

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	208	231	213
Units: Percentage of participants
number (confidence interval 95%)
Gaining ≥15 Letters	32.9 (26.7 to 39.0)	29.4 (23.9 to 34.9)	32.7 (26.5 to 38.8)
Gaining ≥10 Letters	58.3 (51.8 to 64.8)	55.5 (49.3 to 61.7)	56.1 (49.6 to 62.5)
Gaining ≥5 Letters	81.8 (76.5 to 87.0)	79.6 (74.5 to 84.7)	80.6 (75.4 to 85.8)
Gaining ≥0 Letters	93.2 (89.8 to 96.7)	92.2 (88.8 to 95.6)	92.0 (88.4 to 95.6)

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, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

421

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

-8.5

upper limit

8.9

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, TN Population v C: Aflibercept 2 mg Q8W, TN Population

Number of subjects included in analysis

444

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

-11.8

upper limit

4.8

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

421

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-6.9

upper limit

11.4

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

444

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

-9.8

upper limit

8.1

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

421

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

-6.2

upper limit

8.5

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

444

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

-8.3

upper limit

6.2

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

421

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

-3.8

upper limit

6.2

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

444

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

-4.8

upper limit

5.2

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	254	254 ^[14]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 245,243,242)	13.9 (9.7 to 18.0)	10.7 (7.0 to 14.4)	10.3 (6.6 to 14.1)
Week 8 (n = 244,246,242)	14.7 (10.3 to 19.1)	17.9 (13.2 to 22.5)	15.7 (11.2 to 20.1)
Week 12 (n = 242,241,236)	19.9 (15.0 to 24.8)	23.2 (18.1 to 28.3)	19.7 (14.8 to 24.6)
Week 16 (n = 241,241,230)	23.3 (18.0 to 28.5)	26.0 (20.8 to 31.2)	23.5 (18.2 to 28.7)
Week 20 (n = 233,239,230)	25.9 (20.4 to 31.4)	22.7 (17.5 to 27.9)	22.0 (16.9 to 27.1)
Week 24 (n = 231,242,232)	30.2 (24.4 to 35.9)	24.5 (19.2 to 29.7)	24.3 (18.9 to 29.6)
Week 28 (n = 223,232,222)	29.8 (23.9 to 35.6)	28.3 (22.7 to 33.8)	26.5 (20.8 to 32.1)
Week 32 (n = 216,220,216)	34.4 (28.4 to 40.5)	27.9 (22.1 to 33.6)	25.1 (19.6 to 30.7)
Week 36 (n = 212,220,209)	34.1 (28.0 to 40.2)	34.2 (28.3 to 40.1)	28.9 (23.2 to 34.5)
Week 40 (n = 213,222,211)	37.8 (31.4 to 44.1)	32.5 (26.6 to 38.4)	28.4 (22.6 to 34.2)
Week 44 (n = 208,223,211)	36.1 (29.9 to 42.3)	30.4 (24.6 to 36.2)	35.0 (28.7 to 41.2)
Week 48 (n = 199,224,212)	32.8 (26.4 to 39.2)	31.2 (25.5 to 36.9)	31.7 (25.7 to 37.8)
Week 52 (n = 209,223,207)	34.1 (27.9 to 40.3)	32.7 (26.9 to 38.6)	33.9 (27.7 to 40.2)
Week 56 (n = 209,224,200)	39.2 (33.0 to 45.5)	30.6 (24.8 to 36.3)	37.6 (31.1 to 44.2)
Week 60 (n = 208,219,200)	37.4 (31.0 to 43.7)	32.5 (26.5 to 38.4)	36.2 (29.9 to 42.5)
Week 64 (n = 205,228,203)	39.8 (33.5 to 46.1)	31.1 (25.2 to 37.0)	31.9 (25.8 to 38.0)
Week 68 (n = 201,214,200)	36.0 (29.7 to 42.3)	33.4 (27.2 to 39.7)	36.4 (30.0 to 42.8)
Week 72 (n = 191,205,196)	35.1 (28.5 to 41.6)	33.7 (27.5 to 39.9)	34.7 (28.2 to 41.2)
Week 76 (n = 199,216,195)	37.2 (30.9 to 43.6)	32.5 (26.4 to 38.6)	34.5 (28.0 to 40.9)
Week 80 (n = 189,210,193)	40.1 (33.6 to 46.6)	33.8 (27.6 to 40.0)	39.4 (32.8 to 45.9)
Week 84 (n = 194,209,199)	40.1 (33.6 to 46.6)	32.0 (25.9 to 38.1)	39.4 (32.8 to 45.9)
Week 88 (n = 194,211,191)	39.5 (32.9 to 46.1)	29.9 (23.8 to 35.9)	38.4 (31.8 to 45.0)
Week 92 (n = 192,210,188)	42.8 (36.1 to 49.6)	38.0 (31.7 to 44.2)	42.5 (35.6 to 49.4)
Week 96 (n = 190,210,189)	42.9 (36.1 to 49.7)	35.9 (29.8 to 41.9)	35.9 (29.2 to 42.5)
Week 100 (n = 196,213,183)	43.9 (37.1 to 50.8)	33.0 (26.9 to 39.0)	40.9 (34.0 to 47.9)

Notes
[14] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	254	254 ^[15]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 245,243,242)	29.4 (23.9 to 34.9)	28.9 (23.3 to 34.5)	26.9 (21.3 to 32.4)
Week 8 (n = 244,246,242)	38.2 (32.3 to 44.1)	42.2 (36.1 to 48.3)	33.1 (27.2 to 38.9)
Week 12 (n = 242,241,236)	45.2 (39.0 to 51.4)	46.9 (40.7 to 53.1)	43.9 (37.7 to 50.1)
Week 16 (n = 241,241,230)	52.3 (46.2 to 58.5)	51.4 (45.4 to 57.4)	41.7 (35.5 to 48.0)
Week 20 (n = 233,239,230)	53.4 (47.2 to 59.6)	51.1 (44.9 to 57.4)	45.5 (39.2 to 51.8)
Week 24 (n = 231,242,232)	57.8 (51.6 to 64.1)	53.1 (46.9 to 59.2)	49.3 (43.1 to 55.5)
Week 28 (n = 223,232,222)	59.7 (53.4 to 66.1)	53.1 (46.9 to 59.4)	55.3 (49.0 to 61.6)
Week 32 (n = 216,220,216)	61.2 (54.7 to 67.6)	50.6 (44.2 to 57.1)	55.7 (49.2 to 62.1)
Week 36 (n = 212,220,209)	58.8 (52.3 to 65.2)	57.8 (51.5 to 64.0)	59.6 (53.1 to 66.0)
Week 40 (n = 213,222,211)	61.3 (55.0 to 67.7)	56.8 (50.6 to 63.1)	58.5 (52.2 to 64.9)
Week 44 (n = 208,223,211)	61.6 (55.0 to 68.2)	56.8 (50.5 to 63.1)	61.1 (54.7 to 67.4)
Week 48 (n = 199,224,212)	57.4 (50.6 to 64.2)	58.0 (51.7 to 64.2)	58.1 (51.7 to 64.6)
Week 52 (n = 209,223,207)	60.9 (54.4 to 67.4)	61.6 (55.3 to 67.8)	60.0 (53.5 to 66.5)
Week 56 (n = 209,224,200)	61.0 (54.6 to 67.4)	58.6 (52.3 to 64.9)	58.6 (51.9 to 65.3)
Week 60 (n = 208,219,200)	57.9 (51.3 to 64.5)	57.1 (50.8 to 63.5)	56.2 (49.5 to 63.0)
Week 64 (n = 205,228,203)	58.4 (51.8 to 65.0)	56.2 (49.9 to 62.5)	53.7 (46.9 to 60.4)
Week 68 (n = 201,214,200)	58.9 (52.4 to 65.4)	54.4 (47.8 to 61.0)	60.7 (54.0 to 67.3)
Week 72 (n = 191,205,196)	58.4 (51.5 to 65.4)	57.5 (51.0 to 64.1)	59.3 (52.5 to 66.0)
Week 76 (n = 199,216,195)	58.2 (51.5 to 64.9)	54.0 (47.5 to 60.6)	57.5 (50.8 to 64.3)
Week 80 (n = 189,210,193)	60.4 (53.6 to 67.2)	58.1 (51.6 to 64.6)	57.0 (50.2 to 63.9)
Week 84 (n = 194,209,199)	55.9 (49.1 to 62.8)	56.5 (50.0 to 63.1)	57.1 (50.3 to 63.8)
Week 88 (n = 194,211,191)	57.1 (50.3 to 63.9)	53.6 (46.9 to 60.3)	58.8 (52.0 to 65.6)
Week 92 (n = 192,210,188)	58.8 (51.9 to 65.6)	57.0 (50.4 to 63.5)	60.5 (53.7 to 67.2)
Week 96 (n = 190,210,189)	64.7 (58.0 to 71.4)	58.4 (51.9 to 65.0)	59.8 (52.9 to 66.7)
Week 100 (n = 196,213,183)	63.0 (56.5 to 69.5)	55.2 (48.7 to 61.7)	66.2 (59.5 to 72.8)

Notes
[15] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	254	254 ^[16]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 245,243,242)	57.9 (51.8 to 64.1)	62.2 (56.1 to 68.3)	58.3 (52.1 to 64.5)
Week 8 (n = 244,246,242)	65.6 (59.7 to 71.4)	68.3 (62.5 to 74.1)	65.3 (59.3 to 71.2)
Week 12 (n = 242,241,236)	71.1 (65.4 to 76.8)	74.7 (69.2 to 80.2)	72.4 (66.7 to 78.1)
Week 16 (n = 241,241,230)	76.4 (71.1 to 81.7)	75.5 (70.1 to 80.8)	69.1 (63.2 to 75.1)
Week 20 (n = 233,239,230)	76.5 (71.1 to 81.9)	80.4 (75.4 to 85.3)	72.5 (66.8 to 78.3)
Week 24 (n = 231,242,232)	78.0 (72.7 to 83.3)	77.4 (72.2 to 82.6)	72.2 (66.5 to 77.9)
Week 28 (n = 223,232,222)	77.2 (71.7 to 82.7)	79.7 (74.6 to 84.9)	76.9 (71.5 to 82.3)
Week 32 (n = 216,220,216)	81.1 (75.9 to 86.3)	80.0 (74.8 to 85.3)	77.1 (71.6 to 82.6)
Week 36 (n = 212,220,209)	77.4 (71.8 to 83.0)	81.4 (76.2 to 86.5)	79.3 (73.9 to 84.7)
Week 40 (n = 213,222,211)	78.6 (73.1 to 84.0)	79.7 (74.4 to 85.0)	81.5 (76.2 to 86.7)
Week 44 (n = 208,223,211)	83.7 (78.7 to 88.6)	79.3 (74.0 to 84.5)	85.8 (81.1 to 90.5)
Week 48 (n = 199,224,212)	79.9 (74.4 to 85.4)	84.0 (79.2 to 88.7)	79.0 (73.6 to 84.4)
Week 52 (n = 209,223,207)	81.8 (76.6 to 87.0)	80.3 (75.1 to 85.4)	79.4 (73.9 to 84.8)
Week 56 (n = 209,224,200)	78.2 (72.7 to 83.7)	78.7 (73.4 to 84.0)	82.4 (77.2 to 87.7)
Week 60 (n = 208,219,200)	75.1 (69.4 to 80.9)	77.3 (71.8 to 82.8)	80.3 (74.8 to 85.7)
Week 64 (n = 205,228,203)	76.3 (70.5 to 82.1)	79.0 (73.7 to 84.2)	73.0 (66.9 to 79.0)
Week 68 (n = 201,214,200)	75.4 (69.6 to 81.3)	77.6 (72.0 to 83.2)	78.2 (72.6 to 83.9)
Week 72 (n = 191,205,196)	78.4 (72.8 to 84.1)	77.7 (72.1 to 83.4)	77.3 (71.5 to 83.1)
Week 76 (n = 199,216,195)	75.6 (69.7 to 81.5)	76.1 (70.4 to 81.7)	73.6 (67.5 to 79.8)
Week 80 (n = 189,210,193)	75.2 (69.3 to 81.1)	78.2 (72.6 to 83.8)	78.5 (72.7 to 84.2)
Week 84 (n = 194,209,199)	72.3 (66.1 to 78.5)	80.5 (75.2 to 85.9)	76.3 (70.5 to 82.2)
Week 88 (n = 194,211,191)	73.9 (67.8 to 80.0)	75.9 (70.2 to 81.7)	80.6 (75.1 to 86.2)
Week 92 (n = 192,210,188)	73.7 (67.6 to 79.9)	77.4 (71.8 to 83.0)	80.2 (74.5 to 85.9)
Week 96 (n = 190,210,189)	78.7 (73.0 to 84.4)	77.5 (72.0 to 83.0)	76.9 (70.9 to 82.8)
Week 100 (n = 196,213,183)	79.0 (73.4 to 84.6)	78.2 (72.7 to 83.7)	81.7 (76.2 to 87.3)

Notes
[16] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	254	254 ^[17]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 245,243,242)	84.9 (80.5 to 89.3)	88.5 (84.5 to 92.5)	88.8 (84.9 to 92.8)
Week 8 (n = 244,246,242)	89.3 (85.4 to 93.1)	90.6 (87.0 to 94.2)	90.1 (86.3 to 93.9)
Week 12 (n = 242,241,236)	90.1 (86.4 to 93.9)	92.9 (89.7 to 96.1)	90.6 (86.9 to 94.3)
Week 16 (n = 241,241,230)	91.3 (87.7 to 94.8)	90.9 (87.3 to 94.5)	91.3 (87.7 to 94.9)
Week 20 (n = 233,239,230)	91.9 (88.4 to 95.4)	92.9 (89.6 to 96.1)	93.9 (90.9 to 97.0)
Week 24 (n = 231,242,232)	90.9 (87.3 to 94.6)	92.6 (89.3 to 95.9)	92.2 (88.7 to 95.7)
Week 28 (n = 223,232,222)	91.9 (88.4 to 95.5)	95.2 (92.5 to 98.0)	94.5 (91.6 to 97.5)
Week 32 (n = 216,220,216)	91.2 (87.4 to 95.0)	90.5 (86.6 to 94.4)	93.5 (90.2 to 96.8)
Week 36 (n = 212,220,209)	91.5 (87.8 to 95.3)	90.5 (86.7 to 94.4)	96.2 (93.7 to 98.8)
Week 40 (n = 213,222,211)	91.6 (87.9 to 95.3)	92.8 (89.5 to 96.2)	94.8 (91.9 to 97.8)
Week 44 (n = 208,223,211)	91.8 (88.1 to 95.6)	91.5 (87.8 to 95.1)	95.3 (92.4 to 98.1)
Week 48 (n = 199,224,212)	93.5 (90.0 to 96.9)	91.1 (87.5 to 94.8)	92.9 (89.4 to 96.4)
Week 52 (n = 209,223,207)	94.3 (91.1 to 97.4)	91.0 (87.3 to 94.8)	93.3 (89.9 to 96.7)
Week 56 (n = 209,224,200)	93.9 (90.7 to 97.1)	92.4 (89.0 to 95.9)	91.0 (87.1 to 95.0)
Week 60 (n = 208,219,200)	88.5 (84.2 to 92.8)	87.8 (83.4 to 92.1)	93.0 (89.5 to 96.5)
Week 64 (n = 205,228,203)	90.5 (86.5 to 94.4)	89.5 (85.5 to 93.5)	88.5 (84.1 to 92.9)
Week 68 (n = 201,214,200)	89.6 (85.4 to 93.8)	90.7 (86.8 to 94.6)	90.5 (86.4 to 94.5)
Week 72 (n = 191,205,196)	89.1 (84.7 to 93.5)	89.7 (85.6 to 93.9)	87.7 (83.1 to 92.3)
Week 76 (n = 199,216,195)	89.6 (85.5 to 93.8)	88.5 (84.2 to 92.7)	89.7 (85.4 to 94.0)
Week 80 (n = 189,210,193)	86.4 (81.5 to 91.2)	89.7 (85.6 to 93.8)	88.9 (84.4 to 93.3)
Week 84 (n = 194,209,199)	87.6 (83.0 to 92.2)	91.1 (87.3 to 94.9)	88.0 (83.5 to 92.5)
Week 88 (n = 194,211,191)	84.7 (79.7 to 89.7)	90.2 (86.2 to 94.1)	90.6 (86.4 to 94.7)
Week 92 (n = 192,210,188)	85.5 (80.6 to 90.5)	86.3 (81.7 to 90.9)	88.9 (84.3 to 93.4)
Week 96 (n = 190,210,189)	84.8 (79.8 to 89.9)	87.8 (83.4 to 92.2)	89.3 (84.9 to 93.7)
Week 100 (n = 196,213,183)	85.3 (80.4 to 90.3)	89.0 (84.9 to 93.1)	91.8 (87.8 to 95.7)

Notes
[17] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	268	293	279
Units: Percentage of participants
number (confidence interval 95%)
Avoiding a Loss of ≥15 Letters	98.9 (97.6 to 100.0)	98.7 (97.4 to 100.0)	98.6 (97.2 to 99.9)
Avoiding a Loss of ≥10 Letters	98.1 (96.5 to 99.7)	98.0 (96.4 to 99.6)	98.2 (96.7 to 99.7)
Avoiding a Loss of ≥5 Letters	96.7 (94.5 to 98.8)	97.0 (95.0 to 98.9)	95.4 (93.0 to 97.8)

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 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

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

2.1

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

572

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

-1.8

upper limit

1.9

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

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

2.1

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

572

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

-2.4

upper limit

1.9

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

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

4.5

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

572

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

4.6

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 307, 306, 309)	99.4 (98.5 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)
Week 8 (n = 305, 311, 309)	99.7 (99.1 to 100.0)	100.0 (100.0 to 100.0)	99.7 (99.1 to 100.0)
Week 12 (n = 305, 303, 302)	99.7 (99.0 to 100.0)	99.7 (99.1 to 100.0)	99.7 (99.1 to 100.0)
Week 16 (n = 300,304,296)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	99.7 (99.0 to 100.0)
Week 20 (n = 294,302,295)	99.6 (99.0 to 100.0)	99.3 (98.4 to 100.0)	99.3 (98.4 to 100.0)
Week 24 (n = 293,306,297)	99.3 (98.4 to 100.0)	99.3 (98.4 to 100.0)	99.3 (98.4 to 100.0)
Week 28 (n = 284,295,287)	99.7 (99.0 to 100.0)	99.3 (98.4 to 100.0)	99.0 (97.8 to 100.0)
Week 32 (n = 277,284,280)	98.9 (97.7 to 100.0)	98.9 (97.8 to 100.0)	98.5 (97.2 to 99.9)
Week 36 (n = 275,281,275)	99.3 (98.3 to 100.0)	99.0 (97.9 to 100.0)	98.9 (97.8 to 100.0)
Week 40 (n = 275,286,274)	98.9 (97.6 to 100.0)	98.6 (97.3 to 99.9)	99.3 (98.3 to 100.0)
Week 44 (n = 269,286,272)	99.6 (98.8 to 100.0)	99.0 (97.8 to 100.0)	98.5 (97.2 to 99.9)
Week 48 (n = 255,286,278)	99.6 (98.8 to 100.0)	98.3 (96.8 to 99.8)	99.3 (98.3 to 100.0)
Week 52 (n = 267,281,271)	98.4 (96.9 to 99.9)	98.9 (97.8 to 100.0)	99.6 (99.0 to 100.0)
Week 56 (n = 267,283,261)	98.5 (97.0 to 100.0)	99.3 (98.4 to 100.0)	98.9 (97.6 to 100.0)
Week 60 (n = 261,277,255)	98.8 (97.5 to 100.0)	98.9 (97.7 to 100.0)	98.0 (96.4 to 99.7)
Week 64 (n = 258,290,259)	98.4 (96.9 to 99.9)	98.3 (96.8 to 99.8)	96.9 (94.8 to 99.0)
Week 68 (n = 254,272,255)	98.4 (96.9 to 99.9)	98.2 (96.6 to 99.8)	97.6 (95.8 to 99.5)
Week 72 (n = 245,261,250)	98.9 (97.6 to 100.0)	98.8 (97.6 to 100.0)	97.6 (95.8 to 99.5)
Week 76 (n = 257,273,251)	96.9 (94.8 to 99.0)	98.2 (96.6 to 99.8)	97.6 (95.7 to 99.5)
Week 80 (n = 247,269,250)	96.4 (94.1 to 98.7)	98.1 (96.5 to 99.7)	97.5 (95.6 to 99.5)
Week 84 (n = 253,265,255)	96.2 (93.9 to 98.5)	99.3 (98.3 to 100.0)	97.3 (95.3 to 99.3)
Week 88 (n = 254,267,247)	94.9 (92.2 to 97.6)	98.1 (96.5 to 99.7)	97.6 (95.7 to 99.5)
Week 92 (n = 249,269,242)	96.0 (93.6 to 98.4)	97.4 (95.5 to 99.3)	97.1 (95.0 to 99.2)
Week 96 (n = 244,267,241)	95.5 (92.9 to 98.1)	97.8 (96.0 to 99.5)	98.4 (96.8 to 99.9)
Week 100 (n = 251,271,237)	96.1 (93.7 to 98.4)	96.3 (94.1 to 98.5)	96.1 (93.7 to 98.5)

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 307,306,309)	99.4 (98.5 to 100.0)	99.3 (98.4 to 100.0)	99.4 (98.5 to 100.0)
Week 8 (n = 305,311,309)	99.0 (98.0 to 100.0)	99.4 (98.5 to 100.0)	99.0 (98.0 to 100.0)
Week 12 (n = 305,303,302)	98.7 (97.5 to 99.9)	99.0 (98.0 to 100.0)	99.3 (98.5 to 100.0)
Week 16 (n = 300,304,296)	99.7 (99.0 to 100.0)	99.7 (99.0 to 100.0)	99.3 (98.4 to 100.0)
Week 20 (n = 294,302,295)	98.6 (97.3 to 99.9)	99.0 (97.9 to 100.0)	99.0 (97.9 to 100.0)
Week 24 (n = 293,306,297)	98.2 (96.7 to 99.8)	99.3 (98.4 to 100.0)	98.7 (97.4 to 99.9)
Week 28 (n = 284,295,287)	99.7 (99.0 to 100.0)	99.0 (97.8 to 100.0)	99.0 (97.8 to 100.0)
Week 32 (n = 277,284,280)	98.5 (97.1 to 99.9)	98.6 (97.3 to 99.9)	97.5 (95.7 to 99.2)
Week 36 (n = 275,281,275)	98.9 (97.7 to 100.0)	98.7 (97.4 to 99.9)	98.2 (96.7 to 99.8)
Week 40 (n = 275,286,274)	98.1 (96.5 to 99.7)	97.9 (96.3 to 99.6)	98.6 (97.2 to 99.9)
Week 44 (n = 269,286,272)	98.5 (97.0 to 100.0)	98.6 (97.3 to 100.0)	98.2 (96.6 to 99.7)
Week 48 (n = 255,286,278)	98.4 (96.8 to 99.9)	96.5 (94.5 to 98.6)	98.9 (97.8 to 100.0)
Week 52 (n = 267,281,271)	97.7 (95.9 to 99.5)	98.2 (96.7 to 99.8)	98.6 (97.2 to 99.9)
Week 56 (n = 267,283,261)	98.5 (97.0 to 100.0)	98.6 (97.2 to 99.9)	97.0 (95.0 to 99.0)
Week 60 (n = 261,277,255)	98.0 (96.3 to 99.7)	97.1 (95.2 to 99.1)	96.5 (94.3 to 98.7)
Week 64 (n = 258,290,259)	97.7 (95.9 to 99.5)	97.3 (95.4 to 99.1)	96.5 (94.3 to 98.7)
Week 68 (n = 254,272,255)	96.4 (94.1 to 98.7)	96.3 (94.1 to 98.5)	96.0 (93.6 to 98.4)
Week 72 (n = 245,261,250)	96.4 (94.1 to 98.7)	98.1 (96.4 to 99.7)	97.2 (95.2 to 99.2)
Week 76 (n = 257,273,251)	95.7 (93.2 to 98.1)	97.4 (95.5 to 99.3)	96.8 (94.6 to 99.0)
Week 80 (n = 247,269,250)	95.2 (92.5 to 97.8)	96.7 (94.6 to 98.8)	95.9 (93.4 to 98.3)
Week 84 (n = 253,265,255)	94.6 (91.9 to 97.3)	98.5 (97.1 to 99.9)	95.3 (92.7 to 97.9)
Week 88 (n = 254,267,247)	93.3 (90.3 to 96.4)	97.0 (95.0 to 99.0)	95.1 (92.4 to 97.7)
Week 92 (n = 249,269,242)	93.6 (90.6 to 96.6)	94.8 (92.1 to 97.4)	95.4 (92.9 to 98.0)
Week 96 (n = 244,267,241)	93.4 (90.3 to 96.5)	95.5 (93.0 to 98.0)	95.3 (92.7 to 98.0)
Week 100 (n = 251,271,237)	94.8 (92.2 to 97.5)	94.9 (92.3 to 97.5)	94.8 (92.0 to 97.6)

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, ITT 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, 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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 307, 306, 309)	95.1 (92.8 to 97.5)	97.4 (95.6 to 99.2)	97.7 (96.1 to 99.4)
Week 8 (n = 305, 311, 309)	96.7 (94.7 to 98.7)	97.1 (95.3 to 98.9)	97.1 (95.2 to 98.9)
Week 12 (n = 305, 303, 302)	97.4 (95.6 to 99.2)	96.7 (94.7 to 98.7)	97.0 (95.1 to 98.9)
Week 16 (n = 300,304,296)	97.7 (96.0 to 99.4)	97.7 (96.0 to 99.4)	96.6 (94.6 to 98.7)
Week 20 (n = 294,302,295)	96.9 (95.0 to 98.9)	96.7 (94.7 to 98.7)	97.3 (95.5 to 99.1)
Week 24 (n = 293,306,297)	96.5 (94.4 to 98.6)	96.4 (94.4 to 98.5)	96.4 (94.3 to 98.4)
Week 28 (n = 284,295,287)	96.1 (93.9 to 98.4)	97.3 (95.5 to 99.1)	97.9 (96.3 to 99.5)
Week 32 (n = 277,284,280)	96.4 (94.3 to 98.6)	96.5 (94.4 to 98.6)	95.0 (92.5 to 97.5)
Week 36 (n = 275,281,275)	97.5 (95.7 to 99.3)	96.6 (94.5 to 98.6)	97.5 (95.7 to 99.3)
Week 40 (n = 275,286,274)	96.7 (94.6 to 98.8)	95.9 (93.6 to 98.1)	96.7 (94.7 to 98.8)
Week 44 (n = 269,286,272)	96.3 (94.0 to 98.5)	95.8 (93.5 to 98.1)	96.3 (94.1 to 98.5)
Week 48 (n = 255,286,278)	96.4 (94.2 to 98.7)	95.2 (92.7 to 97.6)	96.1 (93.8 to 98.3)
Week 52 (n = 267,281,271)	96.2 (93.9 to 98.4)	94.7 (92.1 to 97.3)	96.7 (94.5 to 98.8)
Week 56 (n = 267,283,261)	95.6 (93.1 to 98.0)	96.8 (94.7 to 98.8)	96.6 (94.5 to 98.7)
Week 60 (n = 261,277,255)	95.0 (92.3 to 97.6)	94.6 (92.0 to 97.2)	95.3 (92.8 to 97.8)
Week 64 (n = 258,290,259)	95.9 (93.5 to 98.2)	92.8 (89.8 to 95.8)	93.3 (90.3 to 96.3)
Week 68 (n = 254,272,255)	94.8 (92.1 to 97.6)	93.7 (90.8 to 96.6)	94.9 (92.1 to 97.6)
Week 72 (n = 245,261,250)	94.0 (91.0 to 96.9)	94.6 (91.9 to 97.4)	92.9 (89.7 to 96.0)
Week 76 (n = 257,273,251)	93.7 (90.8 to 96.7)	92.3 (89.2 to 95.5)	94.7 (92.0 to 97.5)
Week 80 (n = 247,269,250)	92.4 (89.1 to 95.7)	93.8 (90.9 to 96.6)	93.4 (90.4 to 96.4)
Week 84 (n = 253,265,255)	92.7 (89.6 to 95.8)	93.3 (90.3 to 96.2)	92.9 (89.9 to 96.0)
Week 88 (n = 254,267,247)	89.9 (86.2 to 93.5)	91.7 (88.5 to 95.0)	93.4 (90.4 to 96.5)
Week 92 (n = 249,269,242)	91.7 (88.3 to 95.1)	90.7 (87.3 to 94.2)	92.9 (89.7 to 96.1)
Week 96 (n = 244,267,241)	90.1 (86.4 to 93.8)	91.1 (87.7 to 94.5)	92.8 (89.5 to 96.1)
Week 100 (n = 251,271,237)	91.6 (88.2 to 95.0)	90.4 (87.0 to 93.9)	93.6 (90.5 to 96.7)

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	208	231	213
Units: Percentage of participants
number (confidence interval 95%)
Avoiding a Loss of ≥15 Letters	98.5 (96.9 to 100.0)	98.7 (97.2 to 100.0)	98.6 (97.0 to 100.0)
Avoiding a Loss of ≥10 Letters	98.1 (96.2 to 99.9)	97.8 (96.0 to 99.7)	98.1 (96.3 to 99.9)
Avoiding a Loss of ≥5 Letters	97.6 (95.5 to 99.7)	97.4 (95.4 to 99.4)	96.2 (93.7 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

421

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

-2.3

upper limit

2.2

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

444

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

-2

upper limit

2.2

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

421

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

-2.7

upper limit

2.6

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

444

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

-2.9

upper limit

2.3

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

421

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

-2

upper limit

4.7

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

444

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

-2.1

upper limit

4.4

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	254	254 ^[18]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 245,243,242)	99.6 (98.8 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)
Week 8 (n = 244,246,242)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	99.6 (98.8 to 100.0)
Week 12 (n = 242,241,236)	100.0 (100.0 to 100.0)	99.6 (98.8 to 100.0)	99.6 (98.8 to 100.0)
Week 16 (n = 241,241,230)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	99.6 (98.7 to 100.0)
Week 20 (n = 233,239,230)	100.0 (100.0 to 100.0)	99.2 (98.0 to 100.0)	99.6 (98.7 to 100.0)
Week 24 (n = 231,242,232)	99.2 (98.0 to 100.0)	99.2 (98.0 to 100.0)	99.6 (98.8 to 100.0)
Week 28 (n = 223,232,222)	99.6 (98.8 to 100.0)	99.6 (98.7 to 100.0)	99.1 (97.9 to 100.0)
Week 32 (n = 216,220,216)	98.6 (97.1 to 100.0)	99.1 (97.8 to 100.0)	99.1 (97.8 to 100.0)
Week 36 (n = 212,220,209)	99.0 (97.7 to 100.0)	99.2 (98.1 to 100.0)	99.1 (97.8 to 100.0)
Week 40 (n = 213,222,211)	99.0 (97.7 to 100.0)	99.1 (97.9 to 100.0)	99.5 (98.6 to 100.0)
Week 44 (n = 208,223,211)	99.5 (98.5 to 100.0)	99.1 (97.9 to 100.0)	99.1 (97.8 to 100.0)
Week 48 (n = 199,224,212)	99.5 (98.5 to 100.0)	98.3 (96.6 to 99.9)	99.5 (98.6 to 100.0)
Week 52 (n = 209,223,207)	99.0 (97.6 to 100.0)	98.6 (97.1 to 100.0)	100.0 (100.0 to 100.0)
Week 56 (n = 209,224,200)	98.1 (96.2 to 99.9)	99.1 (97.9 to 100.0)	98.5 (96.9 to 100.0)
Week 60 (n = 208,219,200)	99.0 (97.7 to 100.0)	98.6 (97.1 to 100.0)	98.5 (96.9 to 100.0)
Week 64 (n = 205,228,203)	99.0 (97.7 to 100.0)	98.2 (96.5 to 99.9)	97.0 (94.7 to 99.4)
Week 68 (n = 201,214,200)	99.0 (97.6 to 100.0)	97.7 (95.7 to 99.7)	97.5 (95.4 to 99.7)
Week 72 (n = 191,205,196)	99.5 (98.5 to 100.0)	98.5 (96.9 to 100.0)	97.5 (95.3 to 99.7)
Week 76 (n = 199,216,195)	97.5 (95.3 to 99.7)	98.1 (96.3 to 99.9)	97.9 (95.8 to 99.9)
Week 80 (n = 189,210,193)	96.8 (94.3 to 99.3)	98.1 (96.3 to 99.9)	97.9 (95.8 to 99.9)
Week 84 (n = 194,209,199)	96.9 (94.5 to 99.3)	99.1 (97.9 to 100.0)	97.0 (94.7 to 99.4)
Week 88 (n = 194,211,191)	94.9 (91.8 to 98.0)	98.1 (96.3 to 99.9)	97.4 (95.2 to 99.6)
Week 92 (n = 192,210,188)	96.4 (93.7 to 99.0)	97.2 (94.9 to 99.4)	97.4 (95.1 to 99.6)
Week 96 (n = 190,210,189)	95.3 (92.3 to 98.3)	97.7 (95.7 to 99.7)	98.5 (96.8 to 100.0)
Week 100 (n = 196,213,183)	95.5 (92.6 to 98.4)	96.3 (93.7 to 98.8)	96.7 (94.1 to 99.3)

Notes
[18] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	254	254 ^[19]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 245,243,242)	99.6 (98.8 to 100.0)	99.2 (98.0 to 100.0)	99.2 (98.0 to 100.0)
Week 8 (n = 244,246,242)	99.2 (98.0 to 100.0)	99.2 (98.1 to 100.0)	98.8 (97.4 to 100.0)
Week 12 (n = 242,241,236)	99.2 (98.1 to 100.0)	99.2 (98.1 to 100.0)	99.2 (98.0 to 100.0)
Week 16 (n = 241,241,230)	99.6 (98.8 to 100.0)	99.6 (98.8 to 100.0)	99.1 (97.9 to 100.0)
Week 20 (n = 233,239,230)	98.7 (97.3 to 100.0)	98.8 (97.3 to 100.0)	99.1 (97.9 to 100.0)
Week 24 (n = 231,242,232)	97.8 (95.9 to 99.7)	99.2 (98.0 to 100.0)	99.6 (98.8 to 100.0)
Week 28 (n = 223,232,222)	99.6 (98.8 to 100.0)	99.1 (97.9 to 100.0)	99.1 (97.9 to 100.0)
Week 32 (n = 216,220,216)	98.2 (96.4 to 99.9)	99.1 (97.8 to 100.0)	98.6 (97.0 to 100.0)
Week 36 (n = 212,220,209)	98.6 (97.0 to 100.0)	98.7 (97.3 to 100.0)	98.6 (97.0 to 100.0)
Week 40 (n = 213,222,211)	98.5 (96.9 to 100.0)	98.7 (97.2 to 100.0)	98.6 (97.0 to 100.0)
Week 44 (n = 208,223,211)	98.1 (96.2 to 99.9)	98.7 (97.2 to 100.0)	98.6 (97.0 to 100.0)
Week 48 (n = 199,224,212)	99.0 (97.5 to 100.0)	96.5 (94.1 to 98.9)	99.5 (98.6 to 100.0)
Week 52 (n = 209,223,207)	98.5 (96.9 to 100.0)	97.8 (95.8 to 99.7)	99.0 (97.7 to 100.0)
Week 56 (n = 209,224,200)	98.1 (96.2 to 99.9)	98.7 (97.2 to 100.0)	96.6 (94.1 to 99.1)
Week 60 (n = 208,219,200)	98.5 (96.9 to 100.0)	96.4 (93.9 to 98.8)	97.0 (94.6 to 99.4)
Week 64 (n = 205,228,203)	98.6 (96.9 to 100.0)	96.9 (94.7 to 99.2)	97.0 (94.7 to 99.4)
Week 68 (n = 201,214,200)	97.0 (94.6 to 99.4)	95.4 (92.6 to 98.2)	95.5 (92.6 to 98.4)
Week 72 (n = 191,205,196)	97.9 (95.8 to 99.9)	98.1 (96.2 to 99.9)	97.5 (95.3 to 99.7)
Week 76 (n = 199,216,195)	96.0 (93.2 to 98.7)	97.2 (95.0 to 99.4)	96.4 (93.8 to 99.0)
Week 80 (n = 189,210,193)	95.8 (92.9 to 98.6)	96.3 (93.7 to 98.8)	96.3 (93.6 to 99.0)
Week 84 (n = 194,209,199)	95.9 (92.9 to 98.6)	98.6 (97.1 to 100.0)	95.5 (92.6 to 98.4)
Week 88 (n = 194,211,191)	93.9 (90.5 to 97.2)	96.7 (94.4 to 99.1)	95.3 (92.3 to 98.3)
Week 92 (n = 192,210,188)	93.8 (90.4 to 97.2)	94.8 (91.8 to 97.8)	95.8 (93.0 to 98.6)
Week 96 (n = 190,210,189)	92.7 (89.0 to 96.4)	96.2 (93.6 to 98.8)	95.7 (92.9 to 98.6)
Week 100 (n = 196,213,183)	94.5 (91.3 to 97.6)	94.5 (91.4 to 97.5)	96.1 (93.3 to 98.9)

Notes
[19] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	254	254 ^[20]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 245,243,242)	95.5 (92.9 to 98.1)	97.1 (95.0 to 99.2)	97.5 (95.6 to 99.5)
Week 8 (n = 244,246,242)	96.3 (93.9 to 98.6)	97.1 (95.1 to 99.2)	96.3 (93.9 to 98.7)
Week 12 (n = 242,241,236)	97.5 (95.6 to 99.5)	97.1 (95.0 to 99.2)	97.0 (94.9 to 99.2)
Week 16 (n = 241,241,230)	97.1 (95.0 to 99.2)	98.3 (96.7 to 99.9)	97.0 (94.7 to 99.2)
Week 20 (n = 233,239,230)	96.6 (94.3 to 98.9)	96.2 (93.8 to 98.6)	97.8 (96.0 to 99.7)
Week 24 (n = 231,242,232)	96.1 (93.6 to 98.6)	97.1 (95.1 to 99.2)	97.4 (95.4 to 99.5)
Week 28 (n = 223,232,222)	96.8 (94.5 to 99.1)	97.8 (96.0 to 99.7)	98.2 (96.4 to 99.9)
Week 32 (n = 216,220,216)	96.8 (94.5 to 99.1)	96.4 (93.9 to 98.8)	95.8 (93.1 to 98.5)
Week 36 (n = 212,220,209)	97.2 (95.0 to 99.4)	96.5 (94.1 to 98.9)	98.1 (96.3 to 99.9)
Week 40 (n = 213,222,211)	96.7 (94.3 to 99.1)	96.9 (94.7 to 99.1)	97.2 (95.0 to 99.4)
Week 44 (n = 208,223,211)	96.2 (93.6 to 98.8)	96.0 (93.4 to 98.5)	97.7 (95.6 to 99.7)
Week 48 (n = 199,224,212)	96.4 (93.9 to 99.0)	95.6 (93.0 to 98.3)	96.2 (93.7 to 98.8)
Week 52 (n = 209,223,207)	97.5 (95.4 to 99.7)	94.6 (91.7 to 97.6)	98.0 (96.2 to 99.9)
Week 56 (n = 209,224,200)	96.7 (94.2 to 99.1)	97.8 (95.8 to 99.7)	96.6 (94.1 to 99.1)
Week 60 (n = 208,219,200)	95.7 (92.9 to 98.4)	94.1 (91.1 to 97.2)	95.5 (92.6 to 98.4)
Week 64 (n = 205,228,203)	96.2 (93.7 to 98.8)	92.1 (88.6 to 95.6)	94.1 (90.8 to 97.3)
Week 68 (n = 201,214,200)	95.0 (92.0 to 98.0)	93.0 (89.6 to 96.4)	94.0 (90.7 to 97.3)
Week 72 (n = 191,205,196)	94.8 (91.7 to 97.9)	94.2 (90.9 to 97.4)	92.4 (88.7 to 96.1)
Week 76 (n = 199,216,195)	94.0 (90.7 to 97.3)	93.2 (89.9 to 96.5)	93.8 (90.4 to 97.2)
Week 80 (n = 189,210,193)	92.7 (89.0 to 96.4)	94.5 (91.4 to 97.5)	94.1 (90.8 to 97.5)
Week 84 (n = 194,209,199)	93.8 (90.4 to 97.2)	93.9 (90.7 to 97.1)	93.5 (90.0 to 96.9)
Week 88 (n = 194,211,191)	90.8 (86.7 to 94.8)	92.1 (88.5 to 95.7)	93.7 (90.2 to 97.1)
Week 92 (n = 192,210,188)	91.3 (87.4 to 95.3)	90.6 (86.7 to 94.5)	93.1 (89.4 to 96.7)
Week 96 (n = 190,210,189)	88.5 (84.0 to 93.0)	92.0 (88.4 to 95.7)	93.0 (89.4 to 96.7)
Week 100 (n = 196,213,183)	90.4 (86.3 to 94.5)	91.7 (88.1 to 95.4)	94.5 (91.2 to 97.8)

Notes
[20] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	268	294	279	208	232	213
Units: Percentage of participants
number (confidence interval 95%)	38.3 (32.6 to 44.0)	32.4 (27.2 to 37.6)	33.5 (28.1 to 38.9)	38.1 (31.7 to 44.5)	34.4 (28.5 to 40.4)	35.5 (29.2 to 41.9)

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

547

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

4.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

12.7

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

573

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

-8.8

upper limit

6.2

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

421

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

-6.5

upper limit

11.6

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

445

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

-10

upper limit

7.4

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 307,308,309)	14.7 (11.0 to 18.5)	13.0 (9.4 to 16.7)	13.2 (9.5 to 16.9)
Week 8 (n = 306,313,309)	17.3 (13.1 to 21.5)	20.4 (16.0 to 24.8)	18.1 (13.8 to 22.3)
Week 12 (n = 306,305,302)	23.2 (18.5 to 27.8)	25.5 (20.8 to 30.3)	22.7 (18.1 to 27.3)
Week 16 (n = 301,306,296)	27.3 (22.4 to 32.2)	28.0 (23.2 to 32.8)	25.8 (21.0 to 30.7)
Week 20 (n = 294,304,295)	28.7 (23.7 to 33.8)	24.0 (19.3 to 28.8)	26.5 (21.7 to 31.4)
Week 24 (n = 294,307,297)	33.3 (28.0 to 38.6)	29.1 (24.0 to 34.1)	27.6 (22.6 to 32.6)
Week 28 (n = 285,295,287)	34.9 (29.4 to 40.3)	30.7 (25.6 to 35.8)	28.8 (23.6 to 34.0)
Week 32 (n = 278,284,280)	39.0 (33.5 to 44.6)	30.4 (25.2 to 35.7)	27.5 (22.4 to 32.6)
Week 36 (n = 275,282,275)	36.3 (30.9 to 41.8)	35.8 (30.4 to 41.2)	33.2 (27.9 to 38.5)
Week 40 (n = 276,287,274)	41.0 (35.3 to 46.6)	34.2 (28.9 to 39.5)	34.5 (29.0 to 40.0)
Week 44 (n = 270,287,272)	40.6 (35.0 to 46.3)	33.5 (28.1 to 38.8)	38.5 (32.9 to 44.1)
Week 48 (n = 255,287,278)	36.6 (30.8 to 42.4)	32.6 (27.4 to 37.8)	33.9 (28.4 to 39.3)
Week 52 (n = 268,282,271)	39.3 (33.7 to 45.0)	34.7 (29.3 to 40.2)	38.4 (32.7 to 44.1)
Week 56 (n = 268,284,261)	43.4 (37.7 to 49.2)	33.2 (27.9 to 38.5)	40.3 (34.4 to 46.2)
Week 60 (n = 262,277,255)	41.2 (35.3 to 47.0)	34.2 (28.8 to 39.6)	39.0 (33.2 to 44.8)
Week 64 (n = 258,291,259)	44.4 (38.5 to 50.2)	31.6 (26.4 to 36.8)	35.0 (29.4 to 40.7)
Week 68 (n = 255,273,255)	40.2 (34.4 to 46.0)	33.5 (27.9 to 39.0)	39.0 (33.2 to 44.8)
Week 72 (n = 246,262,250)	41.0 (35.0 to 47.1)	34.4 (28.8 to 39.9)	36.1 (30.4 to 41.8)
Week 76 (n = 257,274,251)	39.7 (34.0 to 45.5)	35.7 (30.2 to 41.3)	39.1 (33.2 to 44.9)
Week 80 (n = 248,270,250)	43.4 (37.4 to 49.4)	32.8 (27.4 to 38.2)	38.7 (32.7 to 44.6)
Week 84 (n = 253,266,255)	41.7 (35.9 to 47.5)	33.8 (28.2 to 39.4)	40.5 (34.7 to 46.4)
Week 88 (n = 255,268,247)	42.6 (36.8 to 48.4)	32.5 (27.0 to 38.0)	41.7 (35.7 to 47.6)
Week 92 (n = 250,269,242)	45.6 (39.7 to 51.6)	38.3 (32.7 to 43.9)	45.0 (38.9 to 51.2)
Week 96 (n = 245,268,241)	46.0 (39.9 to 52.1)	37.2 (31.7 to 42.7)	40.6 (34.5 to 46.7)
Week 100 (n = 252,272,237)	44.5 (38.4 to 50.5)	34.3 (28.8 to 39.7)	44.3 (38.1 to 50.5)

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	254	254 ^[21]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 245,245,242)	15.1 (10.8 to 19.3)	13.5 (9.4 to 17.6)	12.8 (8.6 to 17.0)
Week 8 (n = 245,248,242)	17.0 (12.4 to 21.7)	22.2 (17.0 to 27.3)	17.7 (13.0 to 22.4)
Week 12 (n = 243,243,236)	22.6 (17.4 to 27.8)	26.3 (21.0 to 31.6)	22.7 (17.6 to 27.9)
Week 16 (n = 242,243,230)	26.1 (20.6 to 31.5)	30.0 (24.4 to 35.5)	26.1 (20.6 to 31.6)
Week 20 (n = 233,241,230)	28.4 (22.7 to 34.1)	26.2 (20.7 to 31.7)	25.9 (20.5 to 31.4)
Week 24 (n = 232,243,232)	34.2 (28.2 to 40.3)	30.5 (24.8 to 36.3)	27.3 (21.7 to 32.9)
Week 28 (n = 224,232,222)	35.4 (29.1 to 41.6)	32.9 (27.0 to 38.9)	29.6 (23.7 to 35.6)
Week 32 (n = 217,220,216)	38.4 (32.0 to 44.7)	31.5 (25.5 to 37.5)	28.9 (23.0 to 34.8)
Week 36 (n = 212,221,209)	37.0 (30.7 to 43.3)	38.0 (31.9 to 44.2)	34.6 (28.5 to 40.8)
Week 40 (n = 214,223,211)	41.4 (34.9 to 47.8)	36.4 (30.2 to 42.5)	34.6 (28.3 to 40.9)
Week 44 (n = 209,224,211)	40.3 (33.8 to 46.7)	34.3 (28.2 to 40.4)	40.7 (34.2 to 47.2)
Week 48 (n = 199,225,212)	36.7 (30.1 to 43.4)	34.9 (28.9 to 40.9)	36.5 (30.1 to 42.9)
Week 52 (n = 210,224,207)	39.1 (32.6 to 45.6)	37.0 (30.8 to 43.2)	39.8 (33.2 to 46.4)
Week 56 (n = 210,225,200)	44.7 (38.1 to 51.2)	35.2 (29.1 to 41.3)	41.7 (35.0 to 48.5)
Week 60 (n = 209,219,200)	40.9 (34.3 to 47.5)	36.9 (30.6 to 43.2)	39.2 (32.7 to 45.8)
Week 64 (n = 205,229,203)	44.0 (37.4 to 50.6)	33.6 (27.5 to 39.7)	35.4 (29.0 to 41.8)
Week 68 (n = 202,215,200)	39.7 (33.2 to 46.2)	35.5 (29.1 to 41.9)	40.0 (33.4 to 46.6)
Week 72 (n = 192,206,196)	40.0 (33.1 to 46.8)	37.7 (31.2 to 44.2)	38.3 (31.7 to 45.0)
Week 76 (n = 199,217,195)	40.6 (34.0 to 47.2)	37.8 (31.4 to 44.2)	39.1 (32.4 to 45.8)
Week 80 (n = 190,211,193)	44.9 (38.0 to 51.8)	37.3 (30.9 to 43.7)	40.9 (34.1 to 47.6)
Week 84 (n = 194,210,199)	43.1 (36.5 to 49.8)	36.0 (29.6 to 42.4)	41.4 (34.8 to 48.1)
Week 88 (n = 195,212,191)	42.3 (35.6 to 49.1)	33.5 (27.2 to 39.8)	41.5 (34.7 to 48.2)
Week 92 (n = 193,210,188)	47.1 (40.2 to 54.0)	42.6 (36.1 to 49.2)	45.2 (38.2 to 52.1)
Week 96 (n = 191,211,189)	44.6 (37.7 to 51.5)	39.5 (33.1 to 45.8)	41.4 (34.4 to 48.3)
Week 100 (n = 197,214,183)	45.6 (38.7 to 52.5)	36.9 (30.6 to 43.2)	44.9 (37.8 to 52.0)

Notes
[21] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	268	293	279	208	231	213
Units: Percentage of participants
number (confidence interval 95%)	73.2 (68.2 to 78.3)	71.6 (66.7 to 76.4)	68.5 (63.6 to 73.5)	73.6 (68.0 to 79.3)	74.2 (68.9 to 79.5)	72.1 (66.6 to 77.7)

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

4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

11.8

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

572

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.1

upper limit

9.8

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

421

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-6.5

upper limit

9.4

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

444

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

-6

upper limit

9.3

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 307,306,309)	56.7 (51.6 to 61.7)	57.8 (53.2 to 62.4)	54.4 (49.7 to 59.1)
Week 8 (n = 305,311,309)	61.3 (56.4 to 66.2)	65.7 (61.1 to 70.3)	59.4 (54.7 to 64.1)
Week 12 (n = 305,303,302)	68.0 (63.2 to 72.8)	67.8 (63.2 to 72.4)	65.2 (60.4 to 70.0)
Week 16 (n = 300,304,296)	66.8 (61.9 to 71.7)	69.2 (64.6 to 73.7)	64.6 (59.7 to 69.6)
Week 20 (n = 294,302,295)	69.6 (64.8 to 74.5)	67.3 (62.5 to 72.0)	66.0 (61.2 to 70.7)
Week 24 (n = 293,306,297)	70.6 (65.7 to 75.6)	69.1 (64.4 to 73.8)	65.5 (60.6 to 70.4)
Week 28 (n = 284,295,287)	72.0 (67.1 to 76.9)	69.9 (65.2 to 74.5)	67.0 (62.2 to 71.9)
Week 32 (n = 277,284,280)	72.6 (67.6 to 77.7)	71.9 (67.1 to 76.7)	67.3 (62.4 to 72.2)
Week 36 (n = 275,281,275)	71.4 (66.3 to 76.4)	69.6 (64.6 to 74.5)	70.1 (65.2 to 75.1)
Week 40 (n = 275,286,274)	73.8 (68.9 to 78.6)	70.8 (65.9 to 75.6)	70.4 (65.4 to 75.4)
Week 44 (n = 269,286,272)	73.7 (68.7 to 78.8)	71.1 (66.3 to 75.9)	69.0 (64.0 to 73.9)
Week 48 (n = 255,286,278)	73.1 (67.8 to 78.3)	73.0 (68.1 to 77.9)	67.1 (62.1 to 72.0)
Week 52 (n = 267,281,271)	74.5 (69.5 to 79.5)	69.8 (64.8 to 74.8)	71.0 (66.1 to 75.9)
Week 56 (n = 267,283,261)	74.7 (69.7 to 79.8)	73.4 (68.6 to 78.2)	71.9 (66.8 to 76.9)
Week 60 (n = 261,277,255)	70.3 (64.9 to 75.7)	67.1 (62.0 to 72.3)	69.4 (64.3 to 74.5)
Week 64 (n = 258,290,259)	74.5 (69.5 to 79.6)	68.1 (63.0 to 73.2)	68.2 (63.0 to 73.5)
Week 68 (n = 254,272,255)	71.9 (66.6 to 77.2)	68.4 (63.2 to 73.6)	72.3 (67.2 to 77.4)
Week 72 (n = 245,261,250)	68.8 (63.2 to 74.3)	72.2 (67.2 to 77.3)	66.2 (60.8 to 71.6)
Week 76 (n = 257,273,251)	70.1 (64.8 to 75.5)	69.0 (63.9 to 74.2)	70.7 (65.3 to 76.1)
Week 80 (n = 247,269,250)	72.4 (67.0 to 77.8)	70.9 (65.8 to 76.0)	69.5 (64.0 to 74.9)
Week 84 (n = 253,265,255)	72.7 (67.4 to 78.0)	71.6 (66.5 to 76.8)	71.4 (66.0 to 76.7)
Week 88 (n = 254,267,247)	68.7 (63.3 to 74.2)	70.3 (65.1 to 75.5)	71.3 (65.9 to 76.6)
Week 92 (n = 249,269,242)	71.6 (66.1 to 77.0)	73.5 (68.4 to 78.6)	69.5 (64.0 to 74.9)
Week 96 (n = 244,267,241)	74.9 (69.5 to 80.3)	73.1 (68.0 to 78.2)	73.2 (67.9 to 78.5)
Week 100 (n = 251,271,237)	73.5 (68.1 to 78.9)	70.0 (64.8 to 75.1)	76.4 (71.2 to 81.6)

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

Top of page

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 the 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	254	254 ^[22]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 245,243,242)	57.5 (51.9 to 63.1)	59.9 (54.8 to 64.9)	56.0 (50.7 to 61.4)
Week 8 (n = 244,246,242)	62.3 (56.8 to 67.7)	67.0 (61.9 to 72.1)	59.9 (54.5 to 65.2)
Week 12 (n = 242,241,236)	68.9 (63.6 to 74.1)	70.2 (65.1 to 75.3)	67.5 (62.1 to 73.0)
Week 16 (n = 241,241,230)	66.8 (61.3 to 72.3)	70.7 (65.7 to 75.7)	65.0 (59.4 to 70.6)
Week 20 (n = 233,239,230)	70.2 (64.7 to 75.6)	69.2 (64.0 to 74.3)	67.4 (62.1 to 72.8)
Week 24 (n = 231,242,232)	71.1 (65.6 to 76.5)	71.7 (66.6 to 76.8)	66.2 (60.8 to 71.7)
Week 28 (n = 223,232,222)	73.5 (68.1 to 79.0)	71.0 (65.9 to 76.1)	69.4 (64.0 to 74.8)
Week 32 (n = 216,220,216)	74.3 (68.7 to 80.0)	74.8 (69.4 to 80.1)	70.2 (64.6 to 75.8)
Week 36 (n = 212,220,209)	71.8 (66.0 to 77.5)	71.2 (65.6 to 76.8)	72.4 (66.9 to 77.9)
Week 40 (n = 213,222,211)	74.0 (68.6 to 79.5)	73.7 (68.4 to 79.0)	72.3 (66.7 to 77.9)
Week 44 (n = 208,223,211)	73.8 (68.1 to 79.4)	74.3 (69.1 to 79.6)	73.5 (68.0 to 78.9)
Week 48 (n = 199,224,212)	73.1 (67.3 to 79.0)	76.2 (70.9 to 81.5)	70.5 (65.0 to 75.9)
Week 52 (n = 209,223,207)	73.9 (68.2 to 79.5)	73.3 (67.7 to 78.8)	75.5 (70.1 to 80.9)
Week 56 (n = 209,224,200)	75.9 (70.3 to 81.5)	75.5 (70.3 to 80.7)	74.7 (69.1 to 80.3)
Week 60 (n = 208,219,200)	69.9 (63.9 to 76.0)	70.9 (65.2 to 76.7)	71.5 (65.8 to 77.2)
Week 64 (n = 205,228,203)	73.7 (67.9 to 79.4)	70.6 (65.0 to 76.2)	70.4 (64.5 to 76.2)
Week 68 (n = 201,214,200)	71.8 (65.8 to 77.7)	68.4 (62.5 to 74.3)	73.9 (68.2 to 79.5)
Week 72 (n = 191,205,196)	67.0 (60.6 to 73.3)	73.9 (68.2 to 79.6)	68.6 (62.6 to 74.6)
Week 76 (n = 199,216,195)	70.3 (64.1 to 76.4)	72.1 (66.4 to 77.8)	71.7 (65.7 to 77.8)
Week 80 (n = 189,210,193)	73.2 (67.0 to 79.3)	72.5 (66.8 to 78.3)	72.6 (66.6 to 78.6)
Week 84 (n = 194,211,191)	73.4 (67.4 to 79.4)	72.2 (66.4 to 78.0)	72.5 (66.6 to 78.5)
Week 88 (n = 194,211,191)	68.1 (62.0 to 74.3)	70.4 (64.5 to 76.2)	75.3 (69.3 to 81.2)
Week 92 (n = 192,210,188)	70.5 (64.2 to 76.8)	74.5 (68.6 to 80.4)	73.2 (67.2 to 79.2)
Week 96 (n = 190,210,189)	72.7 (66.4 to 79.0)	74.8 (69.1 to 80.5)	73.8 (67.9 to 79.8)
Week 100 (n = 196,213,183)	71.2 (64.9 to 77.4)	70.7 (64.8 to 76.6)	77.7 (71.9 to 83.5)

Notes
[22] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	268	294	279	208	232	213
Units: Percentage of participants
number (confidence interval 95%)	0.8 (0.0 to 1.8)	0.0 (0.0 to 0.0)	0.7 (0.0 to 1.7)	1.0 (0.0 to 2.3)	0.0 (0.0 to 0.0)	0.5 (0.0 to 1.4)

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

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

1.5

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

573

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

-1.6

upper limit

0.2

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

421

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

-1.1

upper limit

2.1

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

445

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

-1.4

upper limit

0.4

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 307,308,309)	1.6 (0.2 to 3.0)	1.7 (0.2 to 3.1)	0.3 (0.0 to 1.0)
Week 8 (n = 306,313,309)	1.3 (0.0 to 2.6)	0.6 (0.0 to 1.5)	0.3 (0.0 to 1.0)
Week 12 (n = 306,305,302)	1.3 (0.1 to 2.6)	0.7 (0.0 to 1.6)	0.6 (0.0 to 1.5)
Week 16 (n = 301,306,296)	0.3 (0.0 to 1.0)	0.3 (0.0 to 0.9)	0.7 (0.0 to 1.5)
Week 20 (n = 294,304,295)	1.0 (0.0 to 2.2)	0.3 (0.0 to 0.9)	1.0 (0.0 to 2.1)
Week 24 (n = 294,307,297)	0.7 (0.0 to 1.7)	0.3 (0.0 to 1.0)	1.3 (0.1 to 2.6)
Week 28 (n = 285,295,287)	1.1 (0.0 to 2.2)	0.3 (0.0 to 1.0)	0.7 (0.0 to 1.6)
Week 32 (n = 278,284,280)	0.7 (0.0 to 1.7)	1.4 (0.1 to 2.8)	1.1 (0.0 to 2.3)
Week 36 (n = 275,282,275)	0.7 (0.0 to 1.7)	1.3 (0.1 to 2.6)	0.4 (0.0 to 1.0)
Week 40 (n = 276,287,274)	1.1 (0.0 to 2.4)	1.4 (0.1 to 2.7)	1.1 (0.0 to 2.3)
Week 44 (n = 270,287,272)	0.4 (0.0 to 1.1)	1.0 (0.0 to 2.2)	1.1 (0.0 to 2.3)
Week 48 (n = 255,287,278)	0.8 (0.0 to 1.9)	0.7 (0.0 to 1.6)	1.4 (0.1 to 2.7)
Week 52 (n = 268,282,271)	0.4 (0.0 to 1.2)	0.4 (0.0 to 1.1)	1.1 (0.0 to 2.2)
Week 56 (n = 268,284,261)	1.1 (0.0 to 2.4)	1.0 (0.0 to 2.2)	0.8 (0.0 to 1.8)
Week 60 (n = 262,277,255)	1.2 (0.0 to 2.5)	0.7 (0.0 to 1.7)	1.5 (0.1 to 2.9)
Week 64 (n = 258,291,259)	1.2 (0.0 to 2.4)	0.7 (0.0 to 1.6)	2.0 (0.3 to 3.7)
Week 68 (n = 255,273,255)	1.2 (0.0 to 2.5)	1.1 (0.0 to 2.4)	0.4 (0.0 to 1.1)
Week 72 (n = 246,262,250)	1.2 (0.0 to 2.5)	1.9 (0.3 to 3.6)	1.5 (0.1 to 3.0)
Week 76 (n = 257,274,251)	2.7 (0.8 to 4.7)	1.8 (0.2 to 3.4)	2.0 (0.3 to 3.7)
Week 80 (n = 248,270,250)	2.4 (0.6 to 4.3)	2.6 (0.7 to 4.6)	1.6 (0.1 to 3.1)
Week 84 (n = 253,266,255)	2.7 (0.7 to 4.6)	1.2 (0.0 to 2.5)	1.9 (0.3 to 3.5)
Week 88 (n = 255,268,247)	2.3 (0.5 to 4.1)	1.9 (0.3 to 3.4)	1.2 (0.0 to 2.5)
Week 92 (n = 250,269,242)	3.2 (1.0 to 5.4)	0.8 (0.0 to 1.8)	1.6 (0.1 to 3.1)
Week 96 (n = 245,268,241)	2.9 (0.8 to 5.0)	2.3 (0.5 to 4.1)	2.0 (0.3 to 3.7)
Week 100 (n = 252,272,237)	2.7 (0.7 to 4.7)	3.3 (1.2 to 5.5)	2.5 (0.5 to 4.4)

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	254	254 ^[23]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 245,245,242)	2.0 (0.3 to 3.8)	1.7 (0.1 to 3.2)	0.4 (0.0 to 1.2)
Week 8 (n = 245,248,242)	1.6 (0.1 to 3.2)	0.8 (0.0 to 1.9)	0.4 (0.0 to 1.2)
Week 12 (n = 243,243,236)	1.2 (0.0 to 2.6)	0.4 (0.0 to 1.2)	0.8 (0.0 to 2.0)
Week 16 (n = 242,243,230)	0.4 (0.0 to 1.2)	0.4 (0.0 to 1.2)	0.9 (0.0 to 2.0)
Week 20 (n = 233,241,230)	0.9 (0.0 to 2.1)	0.4 (0.0 to 1.2)	0.9 (0.0 to 2.0)
Week 24 (n = 232,243,232)	0.9 (0.0 to 2.1)	0.4 (0.0 to 1.2)	0.8 (0.0 to 2.0)
Week 28 (n = 224,232,222)	1.3 (0.0 to 2.8)	0.4 (0.0 to 1.3)	0.4 (0.0 to 1.3)
Week 32 (n = 217,220,216)	0.9 (0.0 to 2.2)	1.4 (0.0 to 2.9)	0.5 (0.0 to 1.4)
Week 36 (n = 212,221,209)	1.0 (0.0 to 2.3)	1.7 (0.1 to 3.4)	0.5 (0.0 to 1.4)
Week 40 (n = 214,223,211)	1.0 (0.0 to 2.2)	1.8 (0.1 to 3.5)	0.5 (0.0 to 1.4)
Week 44 (n = 209,224,211)	0.5 (0.0 to 1.4)	1.3 (0.0 to 2.8)	0.5 (0.0 to 1.4)
Week 48 (n = 199,225,212)	1.0 (0.0 to 2.4)	0.9 (0.0 to 2.1)	0.5 (0.0 to 1.4)
Week 52 (n = 210,224,207)	0.0 (0.0 to 0.0)	0.5 (0.0 to 1.4)	0.0 (0.0 to 0.0)
Week 56 (n = 210,225,200)	1.4 (0.0 to 3.0)	0.9 (0.0 to 2.0)	1.0 (0.0 to 2.4)
Week 60 (n = 209,219,200)	0.9 (0.0 to 2.2)	0.9 (0.0 to 2.2)	1.0 (0.0 to 2.4)
Week 64 (n = 205,229,203)	0.5 (0.0 to 1.5)	0.9 (0.0 to 2.0)	2.0 (0.1 to 4.0)
Week 68 (n = 202,215,200)	0.5 (0.0 to 1.5)	1.4 (0.0 to 3.0)	0.5 (0.0 to 1.4)
Week 72 (n = 192,206,196)	1.0 (0.0 to 2.4)	1.4 (0.0 to 3.1)	2.0 (0.1 to 3.9)
Week 76 (n = 199,217,195)	2.0 (0.1 to 3.9)	1.8 (0.1 to 3.6)	2.6 (0.4 to 4.7)
Week 80 (n = 190,211,193)	1.6 (0.0 to 3.4)	2.9 (0.6 to 5.2)	1.5 (0.0 to 3.3)
Week 84 (n = 194,210,199)	2.1 (0.1 to 4.1)	1.0 (0.0 to 2.3)	2.0 (0.1 to 3.9)
Week 88 (n = 195,212,191)	1.5 (0.0 to 3.2)	1.9 (0.1 to 3.7)	1.6 (0.0 to 3.3)
Week 92 (n = 193,210,188)	3.2 (0.7 to 5.6)	0.5 (0.0 to 1.5)	2.1 (0.1 to 4.1)
Week 96 (n = 191,211,189)	2.7 (0.4 to 5.0)	2.4 (0.3 to 4.5)	2.0 (0.1 to 4.0)
Week 100 (n = 197,214,183)	3.0 (0.6 to 5.4)	3.8 (1.2 to 6.3)	2.1 (0.1 to 4.1)

Notes
[23] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 280,289,271)	34.5 (29.1 to 39.8)	38.0 (32.5 to 43.6)	34.0 (28.6 to 39.5)
Week 52 (n = 249,261,246)	43.4 (37.4 to 49.4)	43.9 (37.9 to 49.8)	46.2 (40.2 to 52.2)
Week 96 (n = 214,228,203)	53.5 (46.9 to 60.1)	44.3 (37.9 to 50.7)	43.8 (37.2 to 50.4)

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	254	254 ^[24]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 224,230,209)	37.2 (31.1 to 43.3)	39.5 (33.3 to 45.7)	37.3 (31.0 to 43.7)
Week 52 (n = 195,206,192)	46.0 (39.1 to 52.9)	46.2 (39.4 to 53.1)	51.3 (44.4 to 58.2)
Week 96 (n = 161,177,160)	55.2 (47.6 to 62.8)	44.1 (36.9 to 51.4)	48.8 (41.1 to 56.4)

Notes
[24] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 280,289,271)	12.8 (9.0 to 16.7)	17.0 (12.7 to 21.4)	13.4 (9.3 to 17.4)
Week 52 (n = 249,261,246)	16.3 (11.7 to 20.8)	19.2 (14.4 to 24.0)	19.2 (14.4 to 24.0)
Week 96 (n = 214,228,203)	25.1 (19.3 to 30.9)	19.3 (14.2 to 24.5)	21.8 (16.3 to 27.2)

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	254	254 ^[25]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 224,230,209)	14.2 (9.7 to 18.7)	16.6 (11.8 to 21.4)	14.4 (9.6 to 19.1)
Week 52 (n = 195,206,192)	18.9 (13.4 to 24.4)	19.0 (13.6 to 24.3)	21.6 (15.9 to 27.4)
Week 96 (n = 161,177,160)	27.9 (21.0 to 34.8)	19.2 (13.4 to 25.0)	25.7 (19.0 to 32.4)

Notes
[25] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 280,289,271)	3.6 (1.4 to 5.8)	8.3 (5.2 to 11.5)	3.4 (1.2 to 5.5)
Week 52 (n = 249,261,246)	4.1 (1.6 to 6.5)	7.3 (4.1 to 10.4)	4.9 (2.2 to 7.6)
Week 96 (n = 214,228,203)	7.7 (4.1 to 11.2)	7.3 (4.0 to 10.6)	5.3 (2.3 to 8.4)

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	254	254 ^[26]	248
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 224,230,209)	3.6 (1.1 to 6.0)	6.5 (3.3 to 9.7)	3.3 (0.9 to 5.8)
Week 52 (n = 195,206,192)	5.1 (2.0 to 8.1)	6.3 (3.0 to 9.7)	4.6 (1.7 to 7.5)
Week 96 (n = 161,177,160)	9.2 (4.8 to 13.7)	5.6 (2.2 to 9.0)	6.3 (2.5 to 10.0)

Notes
[26] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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	215	221	221	164	176	171
Units: Percentage of participants
number (confidence interval 95%)	0.8 (0.0 to 2.0)	0.9 (0.0 to 2.2)	0.4 (0.0 to 1.3)	0.6 (0.0 to 1.8)	1.2 (0.0 to 2.8)	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

436

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

upper limit

1.8

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

442

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

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

335

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

-0.6

upper limit

1.8

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

347

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

-0.4

upper limit

2.8

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	230	250	236	178	197	182
Units: Percentage of participants
number (confidence interval 95%)	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)	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

466

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

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

486

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

360

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

379

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 ^[27]

End point description

The number analyzed includes all participants in the Arm B: Faricimab 6 mg PTI, Intent-to-Treat (ITT) Population who had not discontinued the study prior to Week 52.

End point type

Secondary

End point timeframe

Week 52

Notes
[27] - 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	308
Units: Percentage of participants
number (confidence interval 95%)
Once Every 4 Weeks	13.3 (9.5 to 17.1)
Once Every 8 Weeks	15.6 (11.5 to 19.6)
Once Every 12 Weeks	20.1 (15.6 to 24.6)
Once Every 16 Weeks	51.0 (45.4 to 56.6)

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

Top of page

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

The number analyzed includes all participants in the Arm B: Faricimab 6 mg PTI, Treatment-Naive (TN) Population who had not discontinued the study prior to Week 52.

End point type

Secondary

End point timeframe

Week 52

End point values	B: Faricimab 6 mg PTI, TN Population
Number of subjects analysed	245
Units: Percentage of participants
number (confidence interval 95%)
Once Every 4 Weeks	11.8 (7.8 to 15.9)
Once Every 8 Weeks	13.9 (9.5 to 18.2)
Once Every 12 Weeks	20.0 (15.0 to 25.0)
Once Every 16 Weeks	54.3 (48.0 to 60.5)

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 ^[28]

End point description

The number analyzed includes all participants in the Arm B: Faricimab 6 mg PTI, Intent-to-Treat (ITT) Population who had not discontinued the study prior to Week 96.

End point type

Secondary

End point timeframe

Week 96

Notes
[28] - 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	287
Units: Percentage of participants
number (confidence interval 95%)
Once Every 4 Weeks	10.1 (6.6 to 13.6)
Once Every 8 Weeks	11.8 (8.1 to 15.6)
Once Every 12 Weeks	13.6 (9.6 to 17.6)
Once Every 16 Weeks	64.5 (58.9 to 70.0)

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

Top of page

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

The number analyzed includes all participants in the Arm B: Faricimab 6 mg PTI, Treatment-Naive (TN) Population who had not discontinued the study prior to Week 96.

End point type

Secondary

End point timeframe

Week 96

End point values	B: Faricimab 6 mg PTI, TN Population
Number of subjects analysed	227
Units: Percentage of participants
number (confidence interval 95%)
Once Every 4 Weeks	9.3 (5.5 to 13.0)
Once Every 8 Weeks	9.7 (5.8 to 13.5)
Once Every 12 Weeks	12.8 (8.4 to 17.1)
Once Every 16 Weeks	68.3 (62.2 to 74.3)

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 ^[29]

End point description

The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 52.

End point type

Secondary

End point timeframe

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

Notes
[29] - 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	308	245
Units: Percentage of participants
number (confidence interval 95%)	64.3 (58.9 to 69.6)	66.9 (61.0 to 72.8)

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

Top of page

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 ^[30]

End point description

The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 96.

End point type

Secondary

End point timeframe

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

Notes
[30] - 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	287	227
Units: Percentage of participants
number (confidence interval 95%)	63.1 (57.5 to 68.7)	65.6 (59.4 to 71.8)

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	317	319	315	254	254	248
Units: microns
arithmetic mean (confidence interval 95%)	-195.8 (-204.1 to -187.5)	-187.6 (-195.8 to -179.5)	-170.1 (-178.3 to -161.8)	-195.0 (-204.2 to -185.9)	-189.4 (-198.3 to -180.4)	-175.1 (-184.2 to -165.9)

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

632

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted mean difference

Point estimate

-25.7

Confidence interval

level

95%

sides

2-sided

lower limit

-37.4

upper limit

-14

Variability estimate

Standard error of the mean

Dispersion value

5.95

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

634

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted mean difference

Point estimate

-17.6

Confidence interval

level

95%

sides

2-sided

lower limit

-29.2

upper limit

-6

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

502

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted mean difference

Point estimate

-20

Confidence interval

level

95%

sides

2-sided

lower limit

-32.9

upper limit

-7

Variability estimate

Standard error of the mean

Dispersion value

6.59

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

502

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted mean difference

Point estimate

-14.3

Confidence interval

level

95%

sides

2-sided

lower limit

-27.1

upper limit

-1.5

Variability estimate

Standard error of the mean

Dispersion value

6.51

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	317	319	315
Units: microns
arithmetic mean (confidence interval 95%)
Week 4	-106.1 (-115.7 to -96.6)	-113.9 (-123.4 to -104.4)	-107.3 (-116.8 to -97.7)
Week 8	-132.0 (-140.9 to -123.0)	-139.6 (-148.4 to -130.8)	-129.6 (-138.5 to -120.6)
Week 12	-146.0 (-154.8 to -137.2)	-155.0 (-163.7 to -146.3)	-143.1 (-151.9 to -134.2)
Week 16	-162.2 (-170.4 to -154.0)	-167.1 (-175.2 to -158.9)	-151.4 (-159.7 to -143.2)
Week 20	-166.8 (-176.0 to -157.6)	-157.2 (-166.3 to -148.1)	-154.6 (-163.8 to -145.4)
Week 24	-179.9 (-188.4 to -171.3)	-181.4 (-189.8 to -173.0)	-146.6 (-155.1 to -138.1)
Week 28	-164.8 (-173.2 to -156.5)	-184.0 (-192.3 to -175.8)	-165.0 (-173.3 to -156.6)
Week 32	-181.9 (-191.4 to -172.4)	-169.4 (-178.9 to -160.0)	-154.8 (-164.3 to -145.3)
Week 36	-170.9 (-179.8 to -162.1)	-189.2 (-197.9 to -180.5)	-168.6 (-177.4 to -159.7)
Week 40	-191.6 (-200.9 to -182.3)	-183.8 (-193.0 to -174.6)	-160.0 (-169.3 to -150.7)
Week 44	-181.7 (-191.0 to -172.3)	-185.9 (-195.1 to -176.7)	-172.3 (-181.7 to -162.9)
Week 48	-195.6 (-205.0 to -186.2)	-184.9 (-194.1 to -175.8)	-162.7 (-172.0 to -153.4)
Week 52	-188.6 (-197.9 to -179.3)	-186.1 (-195.3 to -177.0)	-176.6 (-185.9 to -167.3)
Week 56	-199.0 (-208.4 to -189.7)	-188.5 (-197.7 to -179.4)	-168.2 (-177.5 to -158.8)
Week 60	-194.1 (-204.1 to -184.0)	-186.1 (-195.9 to -176.3)	-179.0 (-189.1 to -168.9)
Week 64	-197.2 (-206.7 to -187.8)	-189.8 (-199.0 to -180.7)	-172.1 (-181.5 to -162.8)
Week 68	-196.2 (-205.2 to -187.1)	-190.3 (-199.2 to -181.5)	-181.4 (-190.4 to -172.4)
Week 72	-202.8 (-212.3 to -193.4)	-191.9 (-201.2 to -182.6)	-172.5 (-181.9 to -163.0)
Week 76	-198.8 (-207.4 to -190.3)	-191.3 (-199.6 to -182.9)	-185.4 (-194.0 to -176.8)
Week 80	-204.0 (-213.4 to -194.6)	-189.7 (-198.8 to -180.5)	-176.7 (-186.1 to -167.3)
Week 84	-198.2 (-207.6 to -188.9)	-197.9 (-207.1 to -188.8)	-185.5 (-194.7 to -176.2)
Week 88	-201.5 (-211.3 to -191.7)	-194.9 (-204.4 to -185.3)	-177.1 (-186.9 to -167.3)
Week 92	-200.5 (-210.2 to -190.9)	-195.4 (-204.7 to -186.1)	-184.0 (-193.7 to -174.4)
Week 96	-206.3 (-215.7 to -196.8)	-199.0 (-208.2 to -189.7)	-180.0 (-189.5 to -170.5)
Week 100	-201.1 (-210.5 to -191.8)	-196.9 (-206.0 to -187.8)	-192.8 (-202.2 to -183.3)

No statistical analyses for this end point

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

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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	254	254 ^[31]	248
Units: microns
arithmetic mean (confidence interval 95%)
Week 4	-106.3 (-116.9 to -95.6)	-112.9 (-123.5 to -102.3)	-106.3 (-117.0 to -95.6)
Week 8	-131.8 (-141.6 to -122.0)	-140.6 (-150.3 to -130.9)	-130.4 (-140.2 to -120.5)
Week 12	-148.8 (-158.4 to -139.2)	-156.6 (-166.2 to -147.1)	-145.3 (-154.9 to -135.6)
Week 16	-163.0 (-171.9 to -154.0)	-168.8 (-177.7 to -159.9)	-157.0 (-166.0 to -148.0)
Week 20	-170.5 (-180.1 to -160.9)	-162.3 (-171.9 to -152.8)	-160.6 (-170.2 to -150.9)
Week 24	-182.4 (-191.5 to -173.3)	-182.9 (-191.9 to -173.9)	-154.6 (-163.8 to -145.5)
Week 28	-166.8 (-175.9 to -157.8)	-183.9 (-192.0 to -174.9)	-174.2 (-183.2 to -165.1)
Week 32	-183.7 (-194.0 to -173.4)	-168.0 (-178.2 to -157.7)	-161.0 (-171.4 to -150.7)
Week 36	-173.8 (-183.5 to -164.1)	-191.5 (-201.1 to -182.0)	-175.6 (-185.2 to -165.9)
Week 40	-191.6 (-201.9 to -181.4)	-186.9 (-197.0 to -176.8)	-165.6 (-175.8 to -155.3)
Week 44	-181.4 (-191.7 to -171.1)	-188.9 (-199.1 to -178.8)	-177.6 (-187.9 to -167.3)
Week 48	-194.5 (-205.1 to -184.0)	-186.8 (-197.1 to -176.6)	-165.8 (-176.3 to -155.4)
Week 52	-188.7 (-198.8 to -178.7)	-186.6 (-196.5 to -176.8)	-181.3 (-191.4 to -171.3)
Week 56	-196.7 (-207.0 to -186.4)	-189.9 (-200.0 to -179.8)	-174.0 (-184.3 to -163.6)
Week 60	-194.3 (-205.6 to -183.0)	-185.2 (-196.3 to -174.1)	-184.1 (-195.5 to -172.7)
Week 64	-196.5 (-207.3 to -185.6)	-191.2 (-201.7 to -180.7)	-175.6 (-186.5 to -164.8)
Week 68	-194.6 (-204.4 to -184.8)	-192.7 (-202.3 to -183.1)	-186.3 (-196.1 to -176.5)
Week 72	-200.9 (-211.0 to -190.8)	-193.4 (-203.3 to -183.5)	-178.0 (-188.1 to -167.9)
Week 76	-200.2 (-209.6 to -190.8)	-192.0 (-201.2 to -182.9)	-190.2 (-199.7 to -180.8)
Week 80	-202.6 (-212.9 to -192.4)	-190.0 (-199.9 to -180.1)	-182.6 (-192.8 to -172.4)
Week 84	-199.3 (-209.8 to -188.7)	-196.0 (-206.3 to -185.8)	-189.5 (-200.0 to -179.0)
Week 88	-200.3 (-211.3 to -189.4)	-195.6 (-206.2 to -184.9)	-181.9 (-192.8 to -170.9)
Week 92	-199.3 (-209.9 to -188.7)	-196.0 (-206.3 to -185.8)	-187.2 (-197.8 to -176.6)
Week 96	-204.5 (-215.1 to -193.8)	-200.8 (-211.1 to -190.4)	-182.9 (-193.5 to -172.2)
Week 100	-200.9 (-211.1 to -190.6)	-198.7 (-208.6 to -188.8)	-193.5 (-203.8 to -183.2)

Notes
[31] - One subject was excluded from the TN Population due to a late report of prior anti-VEGF treatment.

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

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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	268	294	279	208	232	213
Units: Percentage of participants
number (confidence interval 95%)	85.5 (81.3 to 89.7)	81.5 (77.1 to 85.9)	73.2 (68.0 to 78.3)	86.0 (81.3 to 90.7)	83.2 (78.4 to 88.0)	77.0 (71.3 to 82.6)

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

12.3

Confidence interval

level

95%

sides

2-sided

lower limit

5.7

upper limit

18.9

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

573

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

8.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

14.9

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

421

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

1.6

upper limit

16.3

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

445

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Difference in CMH Weighted Percentage

Point estimate

6.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

13.6

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

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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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 309,308,308)	38.2 (32.8 to 43.6)	43.5 (38.0 to 49.0)	38.1 (32.8 to 43.5)
Week 8 (n = 304,312,307)	53.3 (47.7 to 58.9)	57.3 (51.9 to 62.7)	47.9 (42.4 to 53.5)
Week 12 (n = 306,304,302)	61.8 (56.5 to 67.2)	64.8 (59.4 to 70.1)	56.4 (50.8 to 62.0)
Week 16 (n = 296,304,294)	69.2 (64.0 to 74.4)	69.1 (63.9 to 74.2)	62.3 (56.8 to 67.8)
Week 20 (n = 294,298,294)	73.8 (68.9 to 78.8)	67.2 (62.0 to 72.4)	67.4 (62.1 to 72.7)
Week 24 (n = 291,302,298)	77.7 (73.0 to 82.4)	77.9 (73.2 to 82.5)	62.4 (57.0 to 67.9)
Week 28 (n = 280,292,286)	72.1 (67.0 to 77.3)	81.2 (76.8 to 85.6)	71.2 (66.1 to 76.4)
Week 32 (n = 277,279,280)	80.2 (75.6 to 84.9)	72.1 (67.0 to 77.3)	67.0 (61.5 to 72.4)
Week 36 (n = 271,279,276)	73.8 (68.7 to 79.0)	83.8 (79.5 to 88.1)	74.6 (69.6 to 79.7)
Week 40 (n = 273,281,275)	86.1 (82.1 to 90.2)	81.5 (77.0 to 86.0)	72.1 (66.9 to 77.3)
Week 44 (n = 269,281,270)	81.5 (76.9 to 86.0)	80.3 (75.7 to 84.9)	76.6 (71.6 to 81.6)
Week 48 (n = 247,281,272)	87.5 (83.4 to 91.6)	82.7 (78.4 to 87.1)	71.0 (65.7 to 76.4)
Week 52 (n = 266,279,271)	83.7 (79.3 to 88.2)	82.1 (77.6 to 86.6)	76.4 (71.5 to 81.4)
Week 56 (n = 263,284,261)	89.5 (85.9 to 93.2)	85.4 (81.4 to 89.5)	72.2 (66.9 to 77.6)
Week 60 (n = 258,273,253)	85.4 (81.1 to 89.6)	86.1 (82.0 to 90.1)	78.8 (73.9 to 83.8)
Week 64 (n = 249,288,258)	87.6 (83.5 to 91.7)	82.8 (78.5 to 87.2)	73.8 (68.5 to 79.0)
Week 68 (n = 252,268,254)	85.0 (80.6 to 89.3)	83.2 (78.8 to 87.6)	78.2 (73.1 to 83.2)
Week 72 (n = 244,260,248)	88.9 (85.1 to 92.8)	82.4 (77.8 to 86.9)	74.6 (69.2 to 80.0)
Week 76 (n = 247,266,247)	88.4 (84.6 to 92.3)	82.2 (77.7 to 86.7)	79.3 (74.3 to 84.4)
Week 80 (n = 243,265,244)	90.0 (86.3 to 93.8)	83.4 (78.9 to 87.8)	76.6 (71.4 to 81.9)
Week 84 (n = 246,261,251)	88.2 (84.2 to 92.2)	85.8 (81.6 to 90.0)	80.3 (75.4 to 85.2)
Week 88 (n = 248,263,245)	89.5 (85.9 to 93.2)	85.0 (80.7 to 89.2)	78.8 (73.8 to 83.9)
Week 92 (n = 246,266,242)	88.4 (84.5 to 92.4)	84.6 (80.3 to 88.9)	80.3 (75.3 to 85.3)
Week 96 (n = 243,263,239)	92.7 (89.5 to 95.8)	88.1 (84.2 to 92.0)	80.0 (74.9 to 85.0)
Week 100 (n = 245,267,233)	90.6 (87.0 to 94.2)	85.5 (81.3 to 89.7)	84.2 (79.6 to 88.8)

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 4 (n = 309,308,308)	12.3 (8.7 to 16.0)	18.5 (14.2 to 22.8)	15.0 (11.0 to 18.9)
Week 8 (n = 304,312,307)	26.2 (21.3 to 31.0)	25.9 (21.1 to 30.8)	22.5 (17.9 to 27.2)
Week 12 (n = 306,304,302)	33.1 (27.9 to 38.3)	36.7 (31.3 to 42.0)	28.2 (23.2 to 33.3)
Week 16 (n = 296,304,294)	38.5 (33.1 to 44.0)	45.0 (39.4 to 50.5)	33.4 (28.0 to 38.8)
Week 20 (n = 294,298,294)	44.3 (38.7 to 49.9)	41.0 (35.5 to 46.5)	38.5 (32.9 to 44.0)
Week 24 (n = 291,302,298)	50.2 (44.6 to 55.8)	52.3 (46.8 to 57.9)	37.0 (31.5 to 42.4)
Week 28 (n = 280,292,286)	45.2 (39.5 to 50.8)	51.9 (46.4 to 57.3)	46.0 (40.3 to 51.8)
Week 32 (n = 277,279,280)	52.3 (46.6 to 58.1)	46.6 (41.0 to 52.3)	42.7 (36.9 to 48.4)
Week 36 (n = 271,279,276)	50.0 (44.2 to 55.7)	59.6 (54.0 to 65.1)	48.8 (42.9 to 54.6)
Week 40 (n = 273,281,275)	61.2 (55.5 to 66.8)	57.7 (52.0 to 63.3)	49.4 (43.6 to 55.2)
Week 44 (n = 269,281,270)	59.9 (54.3 to 65.5)	58.6 (53.0 to 64.1)	53.5 (47.7 to 59.4)
Week 48 (n = 247,281,272)	67.5 (61.7 to 73.2)	58.3 (52.8 to 63.8)	50.2 (44.3 to 56.1)
Week 52 (n = 266,279,271)	64.5 (58.8 to 70.1)	60.9 (55.3 to 66.4)	54.2 (48.4 to 60.1)
Week 56 (n = 263,284,261)	70.3 (64.9 to 75.6)	63.6 (58.2 to 69.1)	51.2 (45.2 to 57.1)
Week 60 (n = 258,273,253)	65.4 (59.8 to 71.1)	65.7 (60.1 to 71.2)	59.2 (53.3 to 65.2)
Week 64 (n = 249,288,258)	71.6 (66.2 to 77.1)	58.7 (53.1 to 64.2)	52.8 (46.8 to 58.7)
Week 68 (n = 252,268,254)	66.9 (61.2 to 72.6)	60.6 (55.0 to 66.2)	59.8 (53.9 to 65.8)
Week 72 (n = 244,260,248)	71.2 (65.6 to 76.7)	65.6 (60.1 to 71.1)	58.8 (52.8 to 64.8)
Week 76 (n = 247,266,247)	68.4 (62.9 to 74.0)	62.8 (57.2 to 68.5)	58.9 (52.9 to 64.9)
Week 80 (n = 243,265,244)	72.6 (67.2 to 78.1)	64.0 (58.4 to 69.7)	60.1 (54.1 to 66.1)
Week 84 (n = 246,261,251)	68.4 (62.8 to 74.0)	67.6 (62.1 to 73.1)	60.7 (54.7 to 66.6)
Week 88 (n = 248,263,245)	71.8 (66.4 to 77.2)	63.3 (57.7 to 68.9)	60.3 (54.2 to 66.4)
Week 92 (n = 246,266,242)	72.9 (67.5 to 78.3)	64.6 (59.0 to 70.2)	64.0 (58.0 to 70.1)
Week 96 (n = 243,263,239)	75.1 (69.9 to 80.3)	67.4 (62.0 to 72.9)	63.1 (57.0 to 69.1)
Week 100 (n = 245,267,233)	72.0 (66.6 to 77.4)	69.3 (63.9 to 74.6)	64.8 (58.8 to 70.9)

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 296,303,294)	19.6 (15.1 to 24.1)	19.8 (15.4 to 24.2)	13.3 (9.4 to 17.1)
Week 48 (n = 246,276,269)	40.9 (34.8 to 47.0)	32.3 (26.9 to 37.7)	22.5 (17.6 to 27.3)
Week 52 (n = 262,280,269)	39.1 (33.3 to 44.9)	35.9 (30.3 to 41.5)	28.4 (23.1 to 33.7)
Week 56 (n = 260,277,258)	42.5 (36.6 to 48.3)	39.9 (34.2 to 45.6)	27.3 (22.0 to 32.7)
Week 92 (n = 240,259,234)	56.0 (49.8 to 62.2)	45.0 (39.0 to 51.0)	39.2 (33.0 to 45.4)
Week 96 (n = 239,256,231)	62.3 (56.3 to 68.4)	47.6 (41.5 to 53.6)	39.1 (32.8 to 45.3)
Week 100 (n = 238,261,229)	56.6 (50.4 to 62.8)	52.2 (46.2 to 58.1)	45.1 (38.7 to 51.4)

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 294,305,293)	99.0 (97.9 to 100.0)	96.7 (94.7 to 98.7)	95.6 (93.3 to 97.8)
Week 48 (n = 251,280,272)	97.2 (95.1 to 99.2)	95.8 (93.5 to 98.1)	95.3 (92.8 to 97.8)
Week 52 (n = 267,281,271)	94.7 (91.9 to 97.4)	95.7 (93.4 to 98.0)	97.8 (96.1 to 99.5)
Week 56 (n = 266,283,263)	97.0 (95.0 to 99.0)	95.8 (93.5 to 98.1)	95.9 (93.5 to 98.2)
Week 92 (n = 245,264,241)	95.0 (92.3 to 97.8)	96.2 (93.9 to 98.5)	96.0 (93.5 to 98.4)
Week 96 (n = 244,263,238)	96.3 (94.0 to 98.7)	96.6 (94.5 to 98.8)	96.2 (93.8 to 98.6)
Week 100 (n = 247,266,233)	96.0 (93.5 to 98.4)	96.2 (93.9 to 98.5)	95.9 (93.5 to 98.3)

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	317	319	315
Units: Percentage of participants
number (confidence interval 95%)
Week 16 (n = 296,303,294)	19.6 (15.1 to 24.1)	19.1 (14.8 to 23.5)	13.3 (9.4 to 17.1)
Week 48 (n = 246,276,269)	40.5 (34.4 to 46.6)	31.2 (25.8 to 36.6)	22.5 (17.6 to 27.3)
Week 52 (n = 262,279,269)	39.1 (33.3 to 44.9)	34.9 (29.4 to 40.5)	28.4 (23.1 to 33.7)
Week 56 (n = 261,277,258)	42.3 (36.4 to 48.2)	39.2 (33.5 to 44.9)	26.6 (21.3 to 31.8)
Week 92 (n = 240,259,234)	55.2 (49.0 to 61.4)	44.2 (38.2 to 50.2)	38.3 (32.2 to 44.5)
Week 96 (n = 239,256,231)	61.0 (54.9 to 67.2)	46.5 (40.4 to 52.5)	38.2 (32.0 to 44.4)
Week 100 (n = 238,262,228)	54.9 (48.7 to 61.2)	51.2 (45.2 to 57.2)	44.8 (38.4 to 51.2)

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	317	319	315
Units: score on a scale
arithmetic mean (confidence interval 95%)
Week 24	5.7 (4.6 to 6.9)	6.5 (5.4 to 7.7)	7.0 (5.9 to 8.1)
Week 52	6.8 (5.5 to 8.2)	6.6 (5.3 to 7.9)	7.6 (6.3 to 9.0)
Week 100	8.8 (7.3 to 10.3)	7.3 (5.9 to 8.7)	6.9 (5.4 to 8.4)

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	317	319	314
Units: Percentage of participants
number (not applicable)
Adverse Event (AE)	89.3	85.3	87.3
Serious AE (SAE)	30.6	25.7	31.8
AE Leading to Withdrawal from Study Treatment	2.2	2.8	1.6
AE of Special Interest (AESI)	7.6	7.2	6.4

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 (IOI).

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	317	319	314
Units: Percentage of participants
number (not applicable)
Study Eye: Adverse Event (AE)	52.4	51.7	44.6
Study Eye: Serious AE (SAE)	4.4	6.3	4.1
Study Eye: AE Leading to Withdrawal from Treatment	0.3	1.9	0.3
Study Eye: Treatment-related AE	3.2	4.4	4.8
Study Eye: Treatment-related SAE	0.0	0.9	0.0
Study Eye: AE of Special Interest (AESI)	4.4	6.3	3.8
Study Eye: AESI, Drop in VA Score ≥30 Letters	3.2	5.0	2.9
Study Eye: AESI, Associated with Severe IOI	0.3	0.0	0.3
StudyEye:AESI,Interv Req to Avoid Perm Vision Loss	0.9	1.3	1.0
Fellow Eye: AE	50.5	43.3	44.3
Fellow Eye: SAE	3.5	1.9	3.5
Fellow Eye: AESI	3.8	0.9	2.9
Fellow Eye: AESI, Drop in VA Score ≥30 Letters	3.5	0.6	2.5
Fellow Eye: AESI, Associated with Severe IOI	0.0	0.0	0.0
FellowEye:AESI,Inter Req to Avoid Perm Vision Loss	0.3	0.3	0.3

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	317	319	314
Units: Percentage of participants
number (not applicable)
Adverse Event (AE)	69.4	68.3	73.6
Serious AE (SAE)	24.0	20.1	28.3
AE Leading to Withdrawal from Study Treatment	1.9	0.9	1.3
AE of Special Interest (AESI)	0.0	0.0	0.0

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 ^[32]

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
[32] - 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	315	319
Units: micrograms per millilitre (μg/mL)
arithmetic mean (standard deviation)
Baseline (n = 298, 305)	0.0001 ( 0.0020 )	0.0000 ( 0.0004 )
Week 4 (n = 284, 287)	0.0192 ( 0.0163 )	0.0196 ( 0.0151 )
Week 28 (n = 266, 283)	0.0030 ( 0.0050 )	0.0115 ( 0.0189 )
Week 52 (n = 248, 270)	0.0042 ( 0.0078 )	0.0113 ( 0.0140 )
Week 76 (n = 237, 250)	0.0060 ( 0.0093 )	0.0060 ( 0.0103 )
Week 100 (n = 254, 267)	0.0058 ( 0.0106 )	0.0071 ( 0.0110 )

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 ^[33]

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. The analysis population consisted of all participants receiving faricimab with at least one determinant post-baseline ADA assessment.

End point type

Secondary

End point timeframe

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

Notes
[33] - 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	313	318
Units: Percentage of participants
number (not applicable)
Total Treatment-Emergent ADA-Positive	7.0	8.2
Treatment-Induced ADA-Positive	7.0	8.2
Treatment-Boosted ADA-Positive	0.0	0.0

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

B: Faricimab 6 mg PTI

Reporting group description

Reporting group title

C: Aflibercept 2 mg Q8W

Reporting group description

Serious adverse events	A: Faricimab 6 mg Q8W	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Total subjects affected by serious adverse events
subjects affected / exposed	97 / 317 (30.60%)	82 / 319 (25.71%)	100 / 314 (31.85%)
number of deaths (all causes)	12	9	10
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Bladder cancer
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Colon cancer
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Hairy cell leukaemia
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Lung neoplasm malignant
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Pancreatic carcinoma
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	1 / 314 (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
Bladder transitional cell carcinoma stage II
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Colorectal cancer metastatic
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Pancreatic carcinoma metastatic
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Pancreatic neoplasm
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Prostate cancer
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	1 / 314 (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
Renal cancer
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Thyroid cancer
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Vascular disorders
Arterial occlusive disease
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Extremity necrosis
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Hypertension
subjects affected / exposed	2 / 317 (0.63%)	0 / 319 (0.00%)	1 / 314 (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
Hypertensive crisis
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Hypotension
subjects affected / exposed	0 / 317 (0.00%)	2 / 319 (0.63%)	1 / 314 (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 / 1
Orthostatic hypotension
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Peripheral arterial occlusive disease
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	1 / 314 (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
Peripheral vascular disorder
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Haematoma
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Surgical and medical procedures
Haemodialysis
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Hospitalisation
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	1 / 314 (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
Inflammation
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Multiple organ dysfunction syndrome
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Necrosis
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Pyrexia
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	2 / 314 (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
Soft tissue inflammation
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Asthenia
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Death
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Generalised oedema
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Hernia obstructive
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Peripheral swelling
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Hypersensitivity
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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	2 / 317 (0.63%)	2 / 319 (0.63%)	2 / 314 (0.64%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	2 / 317 (0.63%)	4 / 319 (1.25%)	0 / 314 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Lung disorder
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Pulmonary fibrosis
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Pulmonary oedema
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Respiratory failure
subjects affected / exposed	2 / 317 (0.63%)	0 / 319 (0.00%)	0 / 314 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Pleuritic pain
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Psychiatric disorders
Delirium
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Depression
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Anxiety
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Confusional state
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Suicide attempt
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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 glucose fluctuation
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Intraocular pressure increased
subjects affected / exposed	2 / 317 (0.63%)	0 / 319 (0.00%)	0 / 314 (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
Biopsy bladder
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
SARS-CoV-2 test positive
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Injury, poisoning and procedural complications
Chemical burns of eye
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Corneal abrasion
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Fall
subjects affected / exposed	0 / 317 (0.00%)	2 / 319 (0.63%)	1 / 314 (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
Femoral neck fracture
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	2 / 314 (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
Femur fracture
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Fracture displacement
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Limb injury
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	0 / 314 (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
Nail avulsion
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Pelvic fracture
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Ankle fracture
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Ligament sprain
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Postoperative ileus
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Rib fracture
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Thermal burn
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Tibia fracture
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Upper limb fracture
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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 disorders
Acute coronary syndrome
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Acute myocardial infarction
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	3 / 314 (0.96%)
occurrences causally related to treatment / all	0 / 1	0 / 1	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Angina pectoris
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	1 / 314 (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
Angina unstable
subjects affected / exposed	1 / 317 (0.32%)	2 / 319 (0.63%)	0 / 314 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aortic valve stenosis
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Arteriosclerosis coronary artery
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Atrial fibrillation
subjects affected / exposed	1 / 317 (0.32%)	2 / 319 (0.63%)	0 / 314 (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
Cardiac arrest
subjects affected / exposed	2 / 317 (0.63%)	1 / 319 (0.31%)	1 / 314 (0.32%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 1
Cardiac failure
subjects affected / exposed	2 / 317 (0.63%)	3 / 319 (0.94%)	4 / 314 (1.27%)
occurrences causally related to treatment / all	0 / 2	0 / 4	1 / 5
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Cardiac failure acute
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Cardiac failure chronic
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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	8 / 317 (2.52%)	4 / 319 (1.25%)	2 / 314 (0.64%)
occurrences causally related to treatment / all	0 / 10	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	1 / 314 (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 / 1
Ischaemic cardiomyopathy
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Myocardial infarction
subjects affected / exposed	5 / 317 (1.58%)	3 / 319 (0.94%)	4 / 314 (1.27%)
occurrences causally related to treatment / all	0 / 5	1 / 3	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 2
Myocardial ischaemia
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	1 / 314 (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
Right ventricular failure
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Subendocardial ischaemia
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Cardio-respiratory arrest
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Chronic left ventricular failure
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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 heart disease
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Nervous system disorders
Cauda equina syndrome
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Cerebral haemorrhage
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Cerebral infarction
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	0 / 314 (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
Cerebrovascular accident
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	4 / 314 (1.27%)
occurrences causally related to treatment / all	0 / 1	0 / 1	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cervical radiculopathy
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Guillain-Barre syndrome
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Lacunar stroke
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolic encephalopathy
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Spinal cord compression
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Syncope
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	2 / 314 (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
Transient ischaemic attack
subjects affected / exposed	2 / 317 (0.63%)	0 / 319 (0.00%)	1 / 314 (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
Encephalopathy
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	1 / 314 (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
Ischaemic stroke
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	3 / 314 (0.96%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Lacunar infarction
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Leukoencephalopathy
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Monoplegia
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Status epilepticus
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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	1 / 317 (0.32%)	2 / 319 (0.63%)	3 / 314 (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
Microcytic anaemia
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Lymphadenopathy mediastinal
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Eye disorders
Cataract
subjects affected / exposed	4 / 317 (1.26%)	7 / 319 (2.19%)	7 / 314 (2.23%)
occurrences causally related to treatment / all	0 / 5	1 / 7	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cataract subcapsular
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	1 / 314 (0.32%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic retinal oedema
subjects affected / exposed	7 / 317 (2.21%)	2 / 319 (0.63%)	1 / 314 (0.32%)
occurrences causally related to treatment / all	0 / 10	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic retinopathy
subjects affected / exposed	0 / 317 (0.00%)	2 / 319 (0.63%)	3 / 314 (0.96%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dry eye
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Eye haemorrhage
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Macular fibrosis
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	1 / 314 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Retinal tear
subjects affected / exposed	0 / 317 (0.00%)	2 / 319 (0.63%)	0 / 314 (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
Retinal vein occlusion
subjects affected / exposed	0 / 317 (0.00%)	2 / 319 (0.63%)	0 / 314 (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
Visual acuity reduced
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	1 / 314 (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
Visual impairment
subjects affected / exposed	0 / 317 (0.00%)	2 / 319 (0.63%)	0 / 314 (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
Vitreous haemorrhage
subjects affected / exposed	4 / 317 (1.26%)	1 / 319 (0.31%)	2 / 314 (0.64%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Angle closure glaucoma
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Cataract nuclear
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	1 / 314 (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
Diabetic eye disease
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Iridocyclitis
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Open angle glaucoma
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Optic ischaemic neuropathy
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Posterior capsule opacification
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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 artery occlusion
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	1 / 314 (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
Retinal degeneration
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Vitreous detachment
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Colitis
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Gastrointestinal dysplasia
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	0 / 314 (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
Impaired gastric emptying
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Rectal haemorrhage
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Anorectal varices
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Intra-abdominal haematoma
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Oesophageal varices haemorrhage
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Hepatobiliary disorders
Bile duct stenosis
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Cholecystitis
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	1 / 314 (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
Cholelithiasis
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	1 / 314 (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
Skin and subcutaneous tissue disorders
Diabetic foot
subjects affected / exposed	0 / 317 (0.00%)	2 / 319 (0.63%)	2 / 314 (0.64%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	4 / 317 (1.26%)	4 / 319 (1.25%)	4 / 314 (1.27%)
occurrences causally related to treatment / all	0 / 4	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Azotaemia
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Calculus urinary
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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 kidney disease
subjects affected / exposed	4 / 317 (1.26%)	0 / 319 (0.00%)	3 / 314 (0.96%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Diabetic nephropathy
subjects affected / exposed	2 / 317 (0.63%)	0 / 319 (0.00%)	0 / 314 (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
End stage renal disease
subjects affected / exposed	3 / 317 (0.95%)	1 / 319 (0.31%)	0 / 314 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal cyst
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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	0 / 317 (0.00%)	0 / 319 (0.00%)	3 / 314 (0.96%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract inflammation
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Haematuria
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Nephropathy
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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 impairment
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Endocrine disorders
Hyperplasia adrenal
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Musculoskeletal and connective tissue disorders
Neuropathic arthropathy
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Spondylitis
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Pain in extremity
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Infections and infestations
Anal abscess
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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 bacterial
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	1 / 314 (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
COVID-19 pneumonia
subjects affected / exposed	3 / 317 (0.95%)	1 / 319 (0.31%)	3 / 314 (0.96%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0
Cellulitis
subjects affected / exposed	3 / 317 (0.95%)	1 / 319 (0.31%)	8 / 314 (2.55%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis gangrenous
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Cystitis
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Diabetic foot infection
subjects affected / exposed	4 / 317 (1.26%)	0 / 319 (0.00%)	0 / 314 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic gangrene
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	1 / 314 (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
Diverticulitis
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Endocarditis
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Endophthalmitis
subjects affected / exposed	2 / 317 (0.63%)	1 / 319 (0.31%)	1 / 314 (0.32%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Gallbladder empyema
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Gangrene
subjects affected / exposed	2 / 317 (0.63%)	2 / 319 (0.63%)	1 / 314 (0.32%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Osteomyelitis
subjects affected / exposed	2 / 317 (0.63%)	1 / 319 (0.31%)	3 / 314 (0.96%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	7 / 317 (2.21%)	6 / 319 (1.88%)	5 / 314 (1.59%)
occurrences causally related to treatment / all	0 / 7	0 / 6	0 / 6
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0
Pyelonephritis
subjects affected / exposed	2 / 317 (0.63%)	0 / 319 (0.00%)	0 / 314 (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
Respiratory tract infection
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Sepsis
subjects affected / exposed	5 / 317 (1.58%)	0 / 319 (0.00%)	2 / 314 (0.64%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Urinary tract infection
subjects affected / exposed	1 / 317 (0.32%)	1 / 319 (0.31%)	5 / 314 (1.59%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
COVID-19
subjects affected / exposed	6 / 317 (1.89%)	7 / 319 (2.19%)	4 / 314 (1.27%)
occurrences causally related to treatment / all	0 / 6	0 / 8	0 / 4
deaths causally related to treatment / all	0 / 3	0 / 1	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	2 / 314 (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
Kidney infection
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Localised infection
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	1 / 314 (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
Lower respiratory tract infection
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Lyme disease
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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
Nasopharyngitis
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Osteomyelitis chronic
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	0 / 314 (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 viral
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Pyoderma
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Septic shock
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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	1 / 317 (0.32%)	0 / 319 (0.00%)	1 / 314 (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
Diabetic endorgan damage
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Diabetic ketoacidosis
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gout
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Hyperkalaemia
subjects affected / exposed	0 / 317 (0.00%)	1 / 319 (0.31%)	2 / 314 (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
Hypoglycaemia
subjects affected / exposed	2 / 317 (0.63%)	3 / 319 (0.94%)	1 / 314 (0.32%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Type 1 diabetes mellitus
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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
Diabetic metabolic decompensation
subjects affected / exposed	1 / 317 (0.32%)	0 / 319 (0.00%)	0 / 314 (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
Failure to thrive
subjects affected / exposed	0 / 317 (0.00%)	0 / 319 (0.00%)	1 / 314 (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	B: Faricimab 6 mg PTI	C: Aflibercept 2 mg Q8W
Total subjects affected by non serious adverse events
subjects affected / exposed	195 / 317 (61.51%)	169 / 319 (52.98%)	178 / 314 (56.69%)
Investigations
Intraocular pressure increased
subjects affected / exposed	21 / 317 (6.62%)	14 / 319 (4.39%)	15 / 314 (4.78%)
occurrences all number	34	23	27
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	18 / 317 (5.68%)	8 / 319 (2.51%)	14 / 314 (4.46%)
occurrences all number	23	8	19
Vascular disorders
Hypertension
subjects affected / exposed	20 / 317 (6.31%)	26 / 319 (8.15%)	16 / 314 (5.10%)
occurrences all number	22	29	16
Nervous system disorders
Headache
subjects affected / exposed	18 / 317 (5.68%)	11 / 319 (3.45%)	8 / 314 (2.55%)
occurrences all number	36	16	10
Eye disorders
Cataract
subjects affected / exposed	52 / 317 (16.40%)	58 / 319 (18.18%)	33 / 314 (10.51%)
occurrences all number	77	88	48
Conjunctival haemorrhage
subjects affected / exposed	36 / 317 (11.36%)	24 / 319 (7.52%)	25 / 314 (7.96%)
occurrences all number	44	29	34
Diabetic retinal oedema
subjects affected / exposed	29 / 317 (9.15%)	25 / 319 (7.84%)	23 / 314 (7.32%)
occurrences all number	31	30	27
Vitreous detachment
subjects affected / exposed	19 / 317 (5.99%)	18 / 319 (5.64%)	27 / 314 (8.60%)
occurrences all number	26	21	30
Dry eye
subjects affected / exposed	19 / 317 (5.99%)	22 / 319 (6.90%)	11 / 314 (3.50%)
occurrences all number	34	39	24
Vitreous floaters
subjects affected / exposed	17 / 317 (5.36%)	12 / 319 (3.76%)	18 / 314 (5.73%)
occurrences all number	22	15	21
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	15 / 317 (4.73%)	16 / 319 (5.02%)	10 / 314 (3.18%)
occurrences all number	15	17	10
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	17 / 317 (5.36%)	7 / 319 (2.19%)	3 / 314 (0.96%)
occurrences all number	17	7	3
Infections and infestations
Nasopharyngitis
subjects affected / exposed	30 / 317 (9.46%)	27 / 319 (8.46%)	38 / 314 (12.10%)
occurrences all number	35	34	43
Urinary tract infection
subjects affected / exposed	14 / 317 (4.42%)	15 / 319 (4.70%)	27 / 314 (8.60%)
occurrences all number	20	18	35

More information

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Were there any global substantial amendments to the protocol? Yes

23 Aug 2018

- Protocol GR40398 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. - A China-specific addendum to Protocol GR40398, Version 2 to support the enrollment of patients from China (in both the global and China extension phases) removed the following optional sample collections from Chinese patients: aqueous humor sample, vitreous sample, PD plasma samples, samples for Research Biosample Repository, and DNA sample.

20 Jun 2019

- The number of patients and sites has been added for the China enrollment plan.; - 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 adverse event 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 serious adverse event or adverse event of special interest, 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 (RHINE)

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 (DRS) Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) at Week 52, ITT and Treatment-Naive Populations

Secondary: Percentage of Participants with a ≥2-Step Diabetic Retinopathy Severity (DRS) Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) 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 (RHINE)