Duchenne Muscular Dystrophy Gene Therapy Continues to Show Efficacy and Safety


Patients demonstrated a 7-point improvement above pre-treatment baselines on the North Star Ambulatory Assessment at 4 years post-treatment.

Sarepta Therapeutics’ SRP-9001 (delandistrogene moxeparvovec), an investigational gene therapy for Duchenne muscular dystrophy (DMD) being developed in partnership with Roche, demonstrated improvements on significant functional outcomes with a consistent safety profile, according to newly presented data from multiple studies.1

Twenty participants in SRP-9001-103 (ENDEAVOR, NCT04626674) treated with SRP-9001 showed an improvement of 4 points on the North Star Ambulatory Assessment (NSAA) from pre-therapy baselines at 52 weeks, as well as a 3.8-point (unadjusted means) and 3.2-point (least squared means) improvement compared to a propensity-weighted external control group (P <.0001).

Additionally, 4 patients in Study SRP-9001-101 (NCT03375164) demonstrated a 7-point improvement above pre-treatment baselines on the NSAA, a 9.9-point unadjusted means and 9.4-point least squared means versus a propensity-weighted external control (P = .0125) at 4 years. An integrated analysis of 52 patients across studies SRP-9001-101, SRP-9001-102 (NCT03769116), and SRP-9001-103 also showed that at 1 year, patients treated with SRP-9001 at the target dose improved 3.1 points (unadjusted means) and 2.4 points (least squared means) on NSAA versus propensity-weighted external control (P <.0001).

“We are absolutely delighted by these most recent results. We now have positive results across multiple studies and multiple time points, including 1-, 2- and 4-years after treatment, and are very pleased with the consistent safety profile across more than 80 treated patients,” Doug Ingram, president and chief executive officer, Sarepta, said in a statement.1 “We are particularly excited about the results of cohort 1 of Study 103, as these results come from our commercially representative process at our intended commercial dose. We robustly powered our 120-patient phase 3 study, known as EMBARK, and the results from Study 103 provide even greater conviction on the powering and probability of success of EMBARK. Duchenne is a relentlessly degenerative disease and every day of delay is a day of muscle and function loss that cannot be recovered. Sarepta and our partner Roche are dedicated and determined to bring this potentially transformative gene therapy to patients around the globe as rapidly as possible.”

The new safety and tolerability data was consistent with past reports on SRP-9001. Vomiting was the most common treatment-related adverse event and observed increases in liver enzymes were transient and responsive to treatment with steroids. One new serious adverse event, a case of myocarditis, appeared in Study 9001-103 and was treated with intravenous (IV) methyl-prednisolone and additional chronic cardiac medications added post-event. At 1 month, a cardiac MRI showed normal function and partial resolution of myocarditic changes, and at 4 months ECHO showed normal systolic function.

“The data from our 103 study is particularly important because it’s from our commercially-representative material,” Louise Rodino-Klapac, PhD, executive vice president and chief scientific officer, Sarepta, said on a conference call regarding the data on July 6, 2022.2 “It can be extremely challenging to achieve the same level of safety and efficacy when scaling up from small-scale to commercial-scale, so we are thrilled to see that these results are not only consistent, but may be improved over previously reported results.”

The on-going global phase 3 Study SRP-9001-301 (EMBARK, NCT05096221) is open to ambulatory male patients aged 4 to 7 with a definitive diagnosis of DMD with a pathogenic frameshift mutation or premature stop codon between exons 18 and 79 (excepting a mutation fully contained within exon 45). Patients must have the ability to cooperate with motor assessment testing. They will additionally be required to be on a stable daily dose of oral corticosteroids for at least 12 weeks prior to screening and throughout the study. Patients who have previously been treated with any gene therapy, investigational medication, or treatment designed to increase dystrophin expression within a certain prior time period to be specified will be excluded from the study.

A total of 120 participants are expected to enroll in the study. In the experimental arm, participants will receive a single IV infusion of SRP-9001 on Day 1 and a single IV infusion of matching placebo at Year 2. In the placebo arm, participants will receive a matching placebo IV infusion on Day 1. They will have the opportunity to receive a single IV infusion of SRP-9001 at Year 2. The primary end point will measure the change from baseline in NSAA total score at 52 weeks. Efficacy-related secondary end points will include a measure of microystrophin protein expression at 12 weeks as measured by western blot, changes from baseline in time to rise to floor, time to complete 100- and 10-meter walk/run, the Timed Stair Ascend 4 Steps test, Stride Velocity 95th Centile, and Patient-Reported Outcomes Measurement Information Score. Safety-related secondary end points will measure the number of participants with a treatment emergent adverse event, serious adverse event, and/or adverse event of special interest.

Additional data from these studies will be presented at the 17th International Congress on Neuromuscular Diseases (ICNMD 2022) in Brussels this week.

1. Sarepta Therapeutics’ investigational gene therapy SRP-9001 for Duchenne muscular dystrophy demonstrates significant functional improvements across multiple studies. News release. Sarepta Therapeutics, Inc. July 6, 2022. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-investigational-gene-therapy-srp-9001 
2. SRP-9001: New clinical data and integrated analysis. Webcast. Sarepta Therapeutics. July 6, 2022. https://investorrelations.sarepta.com/events/event-details/sarepta-therapeutics-share-new-clinical-data-and-integrated-analysis-srp-9001
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