New three-year data from the Phase III EMBARK trial show sustained functional outcomes following a single administration of Elevidys (delandistrogene moxeparvovec) in ambulatory individuals (patients who are still able to walk) aged 4 years and older with Duchenne muscular dystrophy (DMD).
The gene therapy is approved in the US for this patient population, and the updated findings add to the body of post-approval clinical evidence supporting its use.
Sarepta Therapeutics reported that patients treated with the therapy maintained functional performance above baseline three years after dosing. Comparative analyses suggested a slower rate of disease progression versus a matched external control group derived from natural history datasets.
The topline findings were disclosed from EMBARK, a randomized, placebo-controlled study, as part of ongoing post-approval evidence generation for the therapy.
DMD is a rare, inherited neuromuscular disorder caused by mutations in the dystrophin gene. These mutations lead to progressive muscle degeneration and loss of ambulation over time. As of December 2025, Duchenne has been added to the US Recommended Uniform Screening Panel for earlier diagnosis through newborn screening.
Current standards of care rely largely on corticosteroids and supportive interventions and do not directly address the underlying genetic cause of the disease.
Delandistrogene moxeparvovec is a single-dose, adeno-associated virus (AAV)-based gene transfer therapy. It is designed to deliver a transgene encoding micro-dystrophin to skeletal muscle.
Micro-dystrophin is a shortened functional form of dystrophin intended to partially compensate for the absence of full-length dystrophin in patients with DMD.
EMBARK (Study SRP-9001-301) is a multinational Phase III randomized, two-part crossover study. It evaluated the therapy in ambulatory boys with DMD aged 4 to 7 years at enrollment.
In Part 1 of the study, participants were randomized to receive either a single intravenous infusion of delandistrogene moxeparvovec or placebo. In Part 2, patients crossed over, allowing all participants to receive active treatment.
The primary endpoint was changed from baseline in the North Star Ambulatory Assessment total score at Week 52. The assessment is a standardized measure of motor function in ambulatory Duchenne patients.
The three-year analysis focused on patients treated in Part 1. Their outcomes were compared with those of a pre-specified, propensity-score-weighted external control group drawn from natural history studies.
Functional outcomes assessed included the North Star Ambulatory Assessment, Time to Rise and the 10-meter walk/run. These timed tests are commonly used to evaluate ambulatory performance in DMD.
According to the reported results, patients treated with delandistrogene moxeparvovec had mean North Star Ambulatory Assessment scores that remained above baseline three years after treatment.
Relative to the external control group, the treated cohort showed an estimated 70% or greater reduction in the rate of disease progression as measured by Time to Rise and the 10-meter walk/run.
The difference in functional performance between treated patients and external controls increased between Years 2 and 3.
Topline comparisons showed that treated patients scored an average of 4.39 points higher on the North Star Ambulatory Assessment than external controls, indicating better preserved motor function.
Treated patients also completed the Time to Rise and 10-meter walk/run tests faster, with mean differences of 6.05 seconds and 2.70 seconds, respectively.
At three years, no new treatment-related safety signals were observed. Findings were reported as consistent with the established safety profile of the therapy in ambulatory patients.
Related: FDA Clarifies CMC Flexibility for Cell and Gene Therapies
Elevidys carries a boxed warning for acute serious liver injury and acute liver failure.
Sarepta reported that analyses of crossover-treated patients and additional functional endpoints remain ongoing. Participants from EMBARK are continuing into the EXPEDITION long-term follow-up study.
The long-term study is designed to evaluate safety and efficacy for up to five years following treatment.
Beyond gene therapy approaches, other companies are also pursuing alternative modalities for DMD. Atossa Therapeutics is developing (Z)-endoxifen, an oral small-molecule therapy, for the condition. The candidate has received FDA Orphan Drug and Rare Pediatric Disease designations, with development efforts ongoing.
Separately, Sarepta Therapeutics is advancing additional programs in its precision genetic medicine pipeline outside of Duchenne. These include SRP-1005, an investigational small interfering RNA therapy for Huntington’s disease, for which the company has submitted a clinical trial application to initiate a first-in-human Phase I study.
If you want your company to be featured on Xtalks.com, please email [email protected].
Join or login to leave a comment
JOIN LOGIN