Gene Therapy Continues to Show Efficacy in Duchenne Muscular Dystrophy


The placebo crossover cohort experienced statistically significant improvements in NSAA score over external control.

SRP-9001 (delandistrogene moxeparvovec), an investigational gene therapy from Sarepta Therapeutics, statistically improved motor function in children with Duchenne muscular dystrophy (DMD) compared to placebo, according to new data from the phase 2 Study SRP-9001-102 (Study 102; NCT03769116).1

“We are delighted to report positive results for Part 2 of our blinded, placebo-controlled Study 102 in Duchenne, where the 48-week functional benefits of SRP-9001 in patients dosed at cross-over were statistically significant when compared to pre-specified matched external controls. Furthermore, the safety profile of SRP-9001 remains consistent with the wealth of previous clinical data,” Doug Ingram, president and chief executive officer, Sarepta, said in a statement.1

The ongoing, randomized, double-blind, placebo-controlled clinical trial enrolled 41 children with DMD, 21 of whom were in the placebo crossover cohort, to evaluate SRP-9001. The gene transfer therapy is designed to deliver the micro-dystrophingene to targeted muscle tissue.

Participants in the placebo crossover group (n = 20, age range, 5-8 years) scored a mean of 2.0 points higher on North Star Ambulatory Assessment (NSAA) at 48 weeks compared to external control (n = 103; P = .0009). NSAA scores improved 1.3 points from baseline while scores in the external control group decreased 0.7 points from baseline.

READ MORE: Patient Dies in Phase 1b Mini-Dystrophin Gene Therapy Trial in DMD

SRP-9001 continued to be well-tolerated in this second part of the study, with no new safety signals in previously treated patients, no treatment-related serious adverse events (AEs), deaths, or study discontinuations. The most common AE was vomiting. Study participants continue to be monitored for safety and long-term efficacy.

“Study 102, Part 2 results add to the totality of evidence for SRP-9001 generated thus far ‒ with promising results across multiple clinical trials and more than 80 patients dosed, encompassing a wide range of phenotypes as well as the oldest and heaviest Duchenne patients to be dosed with a full body AAV gene therapy infusion to date. The totality of results that we have seen across our multiple trials bolsters our confidence in the potential disease-modifying benefits of this therapy and reinforces our conviction in the probability of success of EMBARK, our large, phase 3 placebo-controlled global study presently underway and dosing. We are reminded daily that Duchenne is a brutal, life-ending disease and SRP-9001 is the greatest near-term hope we all have to address the need for a therapy that changes the trajectory of this disease. We will continue to move as quickly as possible to bring SRP-9001 to patients in the United States and around the world,” Ingram added to the statement.1

Sarepta announced additional positive data from multiple studies in October 2021, including Study 102, Study SRP-9001-101 (NCT03375164), and Study SRP-9001-103 (ENDEAVOR; NCT04626674).3 In study 101, 4 treated patients improved by an average of 8.6 points on North Star Ambulatory Assessment (NSAA) at 3 years after treatment compared to a matched natural history cohort. In study 102, 12 treated patients had an average difference of +2.9 points on NSAA at 1 year after treatment compared to a matched natural history cohort. In study 103, 11 treated patients in cohort 1 improved by an average of 3.0 points on NSAA 6 months after treatment.

"With 77 patients treated to date, the multi-study development program for SRP-9001 represents the most comprehensive and long-term dataset for a Duchenne muscular dystrophy gene therapy in existence. The totality of evidence shows that SRP-9001 is a significantly differentiated gene therapy product candidate with one-time dosing and a stable tolerability profile, results in robust expression and evidence of sustained functional benefits across our various studies," Ingram said in an earlier statement.2

SRP-9001 will be further evaluated in the phase 3, double-blind, EMBARK study (Study SRP-9001-301), which will be conducted across the US, Europe, and Asia.3 The study plans to enroll 120 participants with DMD between the ages of 4 to 7. Participants with mutations inclusively between exons 1-17 or mutations in exon 45 are not eligible.

1. Sarepta Therapeutics’ gene therapy SRP-9001 shows statistically significant functional improvements compared to pre-specified matched external control in part 2 of study SRP-9001-102 for the treatment of Duchenne muscular dystrophy. News release. Sarepta Therapeutics. January 10, 2022.
2. Sarepta Therapeutics’ SRP-9001 shows sustained functional improvements in multiple studies of patients with Duchenne. News release. Sarepta Therapeutics. October 11, 2021.
3. Sarepta Therapeutics announces initiation of EMBARK, a global pivotal study of SRP-9001, a gene therapy for the treatment of Duchenne Muscular Dystrophy. News release. Sarepta Therapeutics. October 4, 2021.
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