Changes in safety parameters for potential adverse effects of drisapersen in the treatment beyond study period (Continued Treatment phase). These changes included addition of measurements of troponin, fibrinogen, haptoglobin and CRP plus extra measurements of aPTT, cystatin C and ECG recordings, and Addition of echocardiography. Minor formatting and typographical errors to improve the clarity and accuracy of the protocol text. Assessment of drisapersen levels in muscle tissue was to be assessed at the Prosensa laboratory in the remaining material from the muscle biopsy after the results were obtained for the mRNA production and dystrophin expression in the muscle tissue. However, this assessment was not performed as the assay was still being optimized. drisapersen levels in the remaining muscle tissue were to be measured at a later time point and the results reported separately. The anti-dystrophin antibody assay was planned to detect potential IgM and IgG antibodies against dystrophin. IgM antibodies were however not assessed. Different to the original protocol, an assay for IgG but not IgM anti-dystrophin reactivity was performed, because IgM control dystrophin antibodies were not available. Formation of antibodies to dystrophin in blood was to be determined at Visits 13, 25, 37 and 61.

• Enhanced safety monitoring. • Addition of stopping criteria. • Addition of alternative injection sites for drug administration. • Addition of DEXA scans. • Additional muscle biopsy at 12 months. • Dose capping according to weight. • Allowance for intermittent dosing for any subject reaching any of the study stopping criteria. • Addition of a parent questionnaire. • Change in Clinical Research Manager. • Other minor clarification and corrections. The enhanced safety monitoring was to enable the Sponsor to closely monitor for early signs of potentially drug-related hepatotoxicity and nephrotoxicity as well as thrombocytopenia. Enhanced monitoring consisted of more frequent assessments as well as some changes to the parameters themselves e.g. addition of glutamate dehydrogenase, albumin/globulin ratio and PTT (international normalized ratio [INR]). Changes to urinalysis parameters were also made including removal of the dipstick analysis, and addition of quantitative analysis of glucose, albumin, protein, creatinine, 1 microglobulin, protein/creatinine ratio and microscopy of urine sediment for erythrocytes, leukocytes and casts. The requirement for troponin I concentrations (introduced in Amendment 5) was removed as the relationship of any change in troponin levels in DMD patients (which may be very variable) is not understood relative to any cardiac condition (personal communication, Kate Bushby, Professor of Neuromuscular Genetics, Newcastle University), and were considered to be unlikely to be useful in detecting incipient cardiac damage.

Further additions to the enhanced safety monitoring implemented in Amendment 6. •Additional detail for stopping criteria. •Change in dosing regimen for all subjects. •Addition of pre-dose pharmacokinetic sampling on a monthly basis from Visit 85 (or as soon as approval of Amendment 7). Ad hoc pharmacokinetic sampling. •Additional instructions on the assessment of local injection site reactions. •Change in blood volumes. •Additions to safety monitoring. •Muscle function (adjustment in visit schedule) •Other minor clarifications and corrections. The amended dosing regimen involved an 8 week washout period for all subjects (Visits 86-93 inclusive). Subjects were then restarted on an intermittent regimen involving 8 weeks of once weekly treatment followed by 4 weeks off drug. New safety monitoring included addition of blood smear for schistocytes (haematology), kidney injury molecule-1 (KIM-1) and cystatin C (urinalysis) and MCP 1 (inflammatory response). Fibrin split products and D dimer were also to be assessed if predefined criteria were met.

• Extension of the study until 2013. • Change in frequency of efficacy measured in order to reduce the • burden on the subjects. • Change in visit schedule in order to reduce the travel burden on the • families. • Change in blood volumes. • Other minor clarifications and corrections. The frequency of the efficacy measures was changed to every 12 weeks in order to fit in with the new assessment schedule and to assess the effect of the intermittent dosing regimen introduced in Amendment 7. Subjects did not have to return to the hospital for laboratory safety testing during the 4 week treatment break unless there was a medical/safety concern, in which case the subject would be asked to return for further monitoring as determined by the investigator.

•Change in legal sponsorship from Prosensa Therapeutics B.V. to GlaxoSmithKline (implemented on 21 July 2011). •Change in supply of drisapersen. •Change in frequency of cystatin C measurements to enhance safety monitoring (every 4 weeks rather than every 12 weeks). •Other minor clarifications and corrections.

•Enhanced safety monitoring and stopping criteria. •Enhanced monitoring and stopping criteria for inflammation. •Modified stopping criteria for coagulation. •Modified stopping criteria for hepatic toxicity. •Change in primary medical contact. •Change in definition of serious adverse events (SAEs). •Other minor clarifications

•Enhanced safety monitoring and stopping criteria •Enhanced renal monitoring •Modified renal stopping criteria •Clarification to the Disseminated Intravascular Coagulation criteria •Update sponsor signature page •Change in Definition of AEs •Change in study schedule for taking subject height and weight / Parent questionnaire added to flowchart •Option to return to weekly dosing at 6 mg/kg drisapersen

1. Updated protocol title to include intravenous dosing as an alternative route of administration. 2. Inclusion of intravenous dose escalation (0.5 mg/kg, 2.0 mg/kg and 6 mg/kg) over a 4 hour infusion period • Reduction of infusion time to 2 hours • Reduction of infusion time to 1 hour. 3. Added text to better describe the treatment beyond study period • Added text for intravenous administration. 4. Laboratory Safety Parameter Stopping and Follow-up Criteria • Added text for ECG 5. Other minor clarifications and corrections.

The amendment will assess the potential for intravenous dosing of PRO051 as an alternative route of administration. A summary of the changes is provided below. 1. Update sponsor signatory details 2. Increased length of study 3. Adjustment of blood volumes 4. Addition of informed consent for subjects 18 years of age 5. Update to Safety Laboratory: a. removal of several biomarker tests (- exploratory biomarkers not used in clinical practice which have not provided an additional positive effect with respect to safety monitoring) b. renal criteria timing c. removal of echocardiography (acknowledgement that this continues to be part of the subjects’ clinical standard of care) d. removal of DEXA (has been less informative than hoped) e. removal of antibody to dystrophin determination (subjects have now had long term exposure without positive antibodies to dystrophin, so extended monitoring not required) 6. Addition of a second central laboratory 7. Other minor clarifications and corrections

Instructions for investigators for subject management during the time period while dosing is on hold per drisapersen Dear Investigator Letter dated 20 September 2013