Lisa Borland, Vice President of Global Medical Affairs at Sarepta Therapeutics, discusses the clinical development program evaluating the safety and efficacy of SRP-9001, an investigational gene transfer therapy for Duchenne muscular dystrophy. Data from this program supported the U.S. Food and Drug Administration’s decision to accept and file a Biologics License Applications (BLA) for SRP-9001, which has a regulatory action date of May 29, 2023.
Duchenne muscular dystrophy is the most common and most severe form of muscular dystrophy. It is caused by mutations in the DMD gene that lead to loss of dystrophin and progressive muscle loss. Symptoms of muscle loss most often appear between the ages of 3 to 5 years, and most children with this disease will be wheelchair dependent by their early teens.
As Ms. Borland explains, SRP-9001 is being evaluated in a clinical development program that currently includes 4 clinical trials: Study 101, Study 102, Study 103 (ENDEAVOR), and Study 301 (EMBARK).
EMBARK is a global, randomized, double-blind, placebo-controlled phase 3 clinical trial of SRP-9001 which has recruited 125 patients with Duchenne muscular dystrophy between the ages of 4 to 7 years. EMBARK is fully enrolled with results expected by the end of 2023. Sarepta has proposed EMBARK as the post-marketing confirmatory trial for SRP-9001.
Safety, protein expression, and functional outcomes are available for Studies 101 and 102, as well as for Cohort 1 of Study 103. Additionally, there is an integrated analysis across these 3 clinical studies comparing functional results to a propensity-score-matched external control at the 1-year mark. The integrated analysis demonstrates robust SRP-9001 protein expression, as well as positive changes in other biological endpoints, such as vector genome copy number.
The analysis also demonstrates the effect of SRP-9001 on functional endpoints, such as North Star Ambulatory Assessment (NSAA) Total Score. As Ms. Borland explains, the NSAA is a validated tool to assess motor function in ambulatory patients with Duchenne muscular dystrophy. Each of the 17 items on the NSAA is scored from 0 to 2. (A score of 0 indicates that a task cannot be performed, a score of 1 indicates that a task can be performed with modification, and a score of 2 indicates that a task can be performed as normal.)
In Cohort 1 of Study 103, which evaluated SRP-9001 in ambulant patients with Duchenne muscular dystrophy between the ages of 4 and 7 years, a mean increase of 4 points on the NSAA was seen in patients treated with SRP-9001 compared to the external control group at 1 year of treatment. As Ms. Borland illustrates, this increase is both statistically and clinically significant.
In Part 1 of Study 102, 2-year data is available. A key finding from this study is that a median increase of 5 points on the NSAA was seen in patients treated with SRP-9001 compared to the external control group.
Finally, in Study 101, Sarepta’s proof-of-concept open-label study for which they have 4 years of data, the 4 patients treated with SRP-9001 had a mean increase of 10 points on the NSAA compared to the external control group. Ms. Borland notes that the patients in Study 101 are now around the age of 9 years and remain ambulatory; this is significant as natural history data suggests these patients would be in a steep decline at this age and would be losing motor function.
For more information about Duchenne muscular dystrophy and other rare musculoskeletal diseases, visit checkrare.com/diseases/musculoskeletal
