Sarepta’s Duchenne Gene Therapy Shows Efficacy in Multiple Studies


Sarepta Therapeutics has also initiated the pivotal phase 3 EMBARK study in pediatric patients with DMD.

SRP-9001, an investigational gene therapy for the potential treatment of Duchenne muscular dystrophy (DMD) from Sarepta Therapeutics, has demonstrated sustained functional improvements in treated patients.1

"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," said Doug Ingram, president and chief executive officer, Sarepta, in a statement.1

Sarepta announced updated data from multiple studies assessing SRP-9001 in pediatric patients, including Study SRP-9001-101 (NCT03375164), Study SRP-9001-102 (NCT03769116), and Study SRP-9001-103 (ENDEAVOR; NCT04626674).

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.

READ MORE: SGT-001 Improves Pulmonary Function in Duchenne Muscular Dystrophy

"When compared to a matched natural history cohort, individuals with Duchenne who received SRP-9001 are performing better on the NSAA or showing stabilization of NSAA scores where we would expect to see a decline. The functional results from Study 103, as early as 6 months following treatment, provide additional confidence in our ability to confirm a treatment effect with SRP-9001 as we advance our pivotal Phase 3 trial," Louise Rodino-Klapac, PhD, executive vice president and chief scientific officer, Sarepta, added to the statement.1 "Given our experience with the AAVrh74 vector in more than 80 individuals with Duchenne and limb-girdle muscular dystrophy, we are very encouraged by the sustained and meaningful clinical results and consistency of the safety profile of SRP-9001."

No new concerning safety events have been observed with SRP-9001 treatment. Treatment-related adverse events (TRAEs) mostly occurred within 90 days of treatment and all resolved. The most common TRAE was vomiting within 1 week of infusion. Transient liver enzyme elevations were observed; these were resolved with steroid treatment. A serious AE was observed in cohort 2 of study 103, in which 1 participant experienced an immune-mediated myositis AE. This AE was specific to the participant’s mutation and was completely resolved following plasmapheresis treatment.

Sarepta also announced that it initiated the phase 3, double-blind, EMBARK study (Study SRP-9001-301) earlier in October, which will be conducted across the US, Europe, and Asia.2 The study plans to enroll 120 participants with DMD between the ages of 4 to 7.1 Participants with mutations inclusively between exons 1-17 or mutations in exon 45 are not eligible. 

"We commence our EMBARK pivotal trial - currently the only truly global Phase 3 trial with a Duchenne gene therapy - with great conviction in the transformative potential of SRP-9001. But while our expression, tolerability, functional evidence and CMC achievements may place SRP-9001 alone among potential therapies, we never forget that we remain in a daily race against a life-ending degenerative disease. To that end, Sarepta, along with our partner Roche, will continue working with tenacity and urgency to bring this potentially transformative treatment to individuals with Duchenne around the world,” Ingram said in the statement.1

The primary end point will be change in NSAA from baseline to week 52 compared to placebo. Secondary endpoints will include skills gained or improved at week 52 as measured by NSAA, microdystrophin expression at week 12 as measured by western blot, timed function tests, and safety. 

In part 1 of the study, treatment and placebo groups will be compared at 52 weeks after treatment. In part 2, the study remains blinded while all participants in placebo begin investigative treatment. All participants will be followed for another 52 weeks.

“The initiation of EMBARK represents the culmination of enormous effort and success from a research, development and manufacturing perspective and is an extraordinarily important moment for the patient community and a leap forward in our effort to change the course of Duchenne,” Ingram said in an earlier statement.2

1. Sarepta Therapeutics’ SRP-9001 shows sustained functional improvements in multiple studies of patients with Duchenne. News release. Sarepta Therapeutics. October 11, 2021.
2. 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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