ELEVIDYS Shows Sustained Functional Differences vs External Controls in Older Ambulatory Duchenne Patients

New data from the 2026 World Muscle Society Annual Congress suggest that delandistrogenemoxeparvovec-rokl (ELEVIDYS; Sarepta Therapeutics), a gene therapy for Duchenne muscular dystrophy (DMD), was associated with better functional outcomes over 2 years in older ambulatory patients compared with matched external controls. Separate findings in children aged 2 to younger than 3 years demonstrated micro-dystrophin expression following treatment, although the analysis did not establish a functional benefit in this younger population.¹

In the older-patient analysis, investigators evaluated 25 ambulatory patients aged 8 to 12 years from the EMBARK and ENDEAVOR studies and compared their outcomes with those of 99 well-matched external controls drawn from DMD natural history datasets. The analysis used a prospectively specified matching approach intended to identify comparable patients and account for key factors that could influence disease progression.

At 2 years, patients treated with ELEVIDYS had significantly better outcomes than external controls across 3 measures of motor function. The least-squares mean difference favored treatment by 3.32 points on the North Star Ambulatory Assessment (NSAA; 95% CI, 1.24-5.41; P = .0022), 0.041 rises per second in time-to-rise-from-floor velocity (95% CI, 0.016-0.066; P = .0019), and 0.195 m/s in 10-meter walk/run velocity (95% CI, 0.046-0.345; P = .0114).¹

The findings are notable because older ambulatory patients with DMD may experience more pronounced functional decline as the disease progresses. However, the comparison relied on external controls rather than a concurrent randomized control group, a limitation to consider when interpreting the results.

“These data are important because they show that we can see a meaningful difference in functional outcomes in older ambulatory patients, even at a stage when disease progression can be more pronounced,” Craig McDonald, MD, professor and chair of the Department of Physical Medicine and Rehabilitation at UC Davis Health and an investigator in the EMBARK and ENDEAVOR studies, said in the company’s announcement.¹

Safety findings in the older ambulatory population were described as consistent with the established safety profile of ELEVIDYS, with nausea and vomiting among the most common treatment-related adverse events.¹The therapy carries a boxed warning for acute serious liver injury and acute liver failure, including life-threatening and fatal cases.

The prescribing information calls for liver function assessment before infusion, systemic corticosteroid treatment before and after infusion, and weekly liver function monitoring for the first 3 months following treatment and until results are unremarkable. Patients are also instructed to remain near an appropriate health care facility for at least 2 months after infusion.Other warnings include serious infections, myocarditis, infusion-related reactions, and immune-mediated myositis. The therapy is contraindicated in patients with any deletion in exon 8 and/or exon 9 of the DMDgene.

Micro-Dystrophin Expression in Children Younger Than 3 Years

A separate analysis evaluated 9 children aged 2 to younger than 3 years from the ENDEAVOR and ENVOL studies. Investigators assessed vector genome copies per nucleus and micro-dystrophin expression following ELEVIDYS administration.¹

In ENDEAVOR, which included 6 children, the mean vector genome copy number was 4.5 (SD, 1.6), and mean micro-dystrophin expression by Western blot was 93.9% of control (SD, 38.2). In ENVOL, which included 3 children, the mean vector genome copy number was 5.3 (SD, 1.9), and mean micro-dystrophin expression was 72.8% of control (SD, 16.9). Micro-dystrophin localization at the sarcolemma was also reported in both analyses.¹

“The findings in younger children help us better understand the biological effects of treatment earlier in the disease course where preserving muscle may offer the greater opportunity for long-term benefit,” said McDonald in a statement.¹ “While measures of expression provide important biological evidence, long-term functional outcomes remain the most meaningful way to understand the impact of treatment for patients and families.”

Together, the analyses add to the evidence being presented on ELEVIDYS across age groups, but the findings address different questions: the older-patient analysis compared functional outcomes with external controls, whereas the younger-patient analysis focused on micro-dystrophin expression.

REFERENCES
1. Sarepta Therapeutics. Sarepta Therapeutics presents new data at 2026 World Muscle Society Annual Congress demonstrating safety and clinically meaningful functional benefit of ELEVIDYS (delandistrogenemoxeparvovec) in older ambulatory patients with Duchenne. Published September 30, 2026. https://www.businesswire.com/news/home/20260930354567/en/Sarepta-Therapeutics-Presents-New-Data-at-2026-World-Muscle-Society-Annual-Congress-Demonstrating-Safety-and-Clinically-Meaningful-Functional-Benefit-of-ELEVIDYS-delandistrogene-moxeparvovec-in-Older-Ambulatory-Patients-with-Duchenne.