WMS 2026: ELEVIDYS shows functional benefit in older ambulatory Duchenne patients – Sarepta
Sarepta Therapeutics, Inc. presented new data at the 31st Annual Congress of the World Muscle Society (WMS) that provide evidence of clinically meaningful functional benefit of ELEVIDYS (delandistrogene moxeparvovec) in older ambulatory patients with Duchenne muscular dystrophy.
In ambulatory patients treated at ages 8 to 12, an age range in which functional decline becomes even more pronounced, treatment was associated with durable benefits across multiple measures over two years compared to a well-matched external control. These findings suggest that the benefits previously observed in younger ambulatory patients are also being observed in older ambulatory patients. Sarepta also presented an analysis of patients treated at ages 2 and 3 that demonstrated robust delandistrogene moxeparvovec-dystrophin expression and sarcolemmal localization 12 weeks after infusion. Together, the analyses expand the evidence base across distinct ages and stages of ambulant Duchenne patients, while continued follow-up will be important to understand longer-term outcomes.
“The period between 8 and 12 years of age represents a critical phase of Duchenne when many boys transition from relative stability to progressive functional decline,” said Louise Rodino-Klapac, Ph.D., president, Research & Development and Technical Operations, Sarepta. “Results presented at WMS 2026 fit within a broader and increasingly consistent body of evidence generated across the clinical development program. Seeing similar patterns emerge across ambulatory Duchenne populations reinforce that timely treatment with delandistrogene moxeparvovec has the potential to meaningfully change the trajectory of the disease. We remain committed to following patients over time and publishing evidence to help inform treatment decisions and advance care for the Duchenne community.”
“The older ambulatory patient data demonstrate that delandistrogene moxeparvovec treatment can provide functional benefit that’s statistically significant at a stage when decline often becomes more pronounced,” said Craig McDonald, M.D., professor and chair of the UC Davis Health Department of Physical Medicine and Rehabilitation, an investigator in the EMBARK and ENDEAVOR studies and an author on both presentations. “In addition, 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. 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.”
Details from the delandistrogene moxeparvovec analyses:
1.103LBP: Functional and safety outcomes in older ambulatory patients with Duchenne muscular dystrophy treated with delandistrogene moxeparvovec (C. McDonald, et al.)
This analysis used a prospectively specified approach to compare treated patients with similar patients from several well-characterized DMD natural history datasets. Patients were matched based on the study eligibility criteria, and the groups were further balanced for key factors that can influence disease progression, with the aims of creating a reliable comparison and addressing common limitations of external control (EC) analyses.
Patients from the EMBARK and ENDEAVOR studies who were aged 8-12 years at time of dosing (n=25), were compared to a well-matched EC group (n=99). Treatment with delandistrogene moxeparvovec demonstrated durable and clinically meaningful functional benefits over two years compared to EC.
Clinically meaningful efficacy was observed across North Star Ambulatory Assessment (NSAA) total score, RFF velocity and 10MWR velocity at 1 and 2 years post-infusion, with nominally statistically significant differences between delandistrogene moxeparvovec-treated and EC patients at Years 1 and 2. Results show a sustained treatment effect and slowing of disease progression and support the use of delandistrogene moxeparvovec in ambulatory patients with DMD aged 8-12 years.
Safety in this patient population was manageable and consistent with the known safety profile of delandistrogene moxeparvovec to date, and the most common treatment related adverse events were nausea and vomiting.
2.080P: Delandistrogene moxeparvovec micro-dystrophin expression and safety in 2–3-year-olds with Duchenne muscular dystrophy in ENDEAVOR and ENVOL studies (C. McDonald, et al.)
In this analysis, ambulatory patients with Duchenne aged ≥2 to <3 years from the ENDEAVOR and ENVOL clinical studies, results demonstrated robust delandistrogene moxeparvovec-dystrophin expression and sarcolemmal localization 12 weeks after infusion with delandistrogene moxeparvovec.
In this patient population, higher overall mean and higher minimum delandistrogene moxeparvovec micro-dystrophin expression was observed compared with previous results in older (≥4 years) ambulatory and non-ambulatory patients. Investigators continue to follow up with patients in order to assess functional outcomes over time and, when available, those results will provide important context for interpreting the clinical benefit in younger patients.
The safety of delandistrogene moxeparvovec in these patients was manageable and consistent with the safety profile to date in ambulatory patients aged 4 years and older.
The use of delandistrogene moxeparvovec in patients under the age of 4 is investigational and its safety and efficacy have not been evaluated by regulatory authorities.
About EMBARK (Study SRP-9001-301)
Study SRP-9001-301, also known as EMBARK, was a multinational, phase 3, randomized, two-part crossover, placebo-controlled study of ELEVIDYS in individuals with Duchenne muscular dystrophy between the ages of 4 to 7 years. The primary endpoint was change from baseline in NSAA Total Score at Week 52 following treatment. Eligible participants received a single dose of ELEVIDYS during either Part 1 or Part 2 of the study.
In Part 1, participants (n=125) were randomized according to age (≥4 to <8 years) or NSAA Total Score at screening (>16 to <29) and received either 1.33 x1014 vg/kg of ELEVIDYS or placebo with a follow-up period for 52 weeks. In Part 2, participants crossed over – meaning, those who were previously treated with placebo in Part 1 received ELEVIDYS and participants who were previously treated with ELEVIDYS received placebo, with a follow-up period for 52 weeks. All patients remained blinded through Part 1 and Part 2.
Secondary outcome measures in EMBARK included the quantity of shortened dystrophin produced by ELEVIDYS at week 12 as measured by western blot in a subset of participants, timed function tests, stride velocity and validated patient reported outcome measures for mobility and upper limb function. One-year results from the Part 1 placebo-controlled period of the EMBARK study were published in Nature Medicine in October 2024. Two-year results were published in Neurology & Therapy in January 2026.
EMBARK was completed at the end of 2024. Following study completion, patients had the option to enroll in EXPEDITION (Study 9001-305), a Phase 3 long-term follow-up study evaluating the safety and efficacy of ELEVIDYS in individuals who previously received the gene therapy. A total of 64 patients received ELEVIDYS in Part 1 of EMBARK, and 52 continue to be followed in EXPEDITION three years after treatment.
About ENDEAVOR (Study 9001-103)
Study SRP-9001-103, also known as ENDEAVOR, is an open-label, Phase 1b study assessing the safety of ELEVIDYS and the expression ELEVIDYS micro-dystrophin in multiple cohorts of male patients with Duchenne. The study has enrolled participants across 8 cohorts and has dosed younger ambulatory individuals aged 2-7 at time of treatment, as well as older ambulant individuals and non-ambulant individuals.
The primary endpoint in ENDEAVOR is the change from baseline in the quantity of ELEVIDYS micro-dystrophin protein expression measured by western blot at 12 weeks. Secondary outcome measures include change from baseline in micro-dystrophin expression measured by percent dystrophin positive fibers at 12 weeks.
About ENVOL (Study 302)
ENVOL is an open-label Phase II study evaluating the safety of Elevidys and expression of Elevidys micro-dystrophin protein in young children. The primary endpoint in ENVOL is safety through five years following treatment, and the secondary outcome measure is change from baseline in the quantity of ELEVIDYS micro-dystrophin protein expression measured by western blot 12 weeks after treatment.
Citation: Mendell, J.R., Muntoni, F., McDonald, C.M. et al. AAV gene therapy for Duchenne muscular dystrophy: the EMBARK phase 3 randomized trial. Nat Med 31, 332–341 (2025). https://doi.org/10.1038/s41591-024-03304-z
Mendell, J.R., Muntoni, F., McDonald, C.M. et al. Two-Year Outcomes Following Delandistrogene Moxeparvovec Treatment in Ambulatory Patients with Duchenne Muscular Dystrophy: Phase 3 EMBARK Trial. Neurol Ther 15, 545–559 (2026). https://doi.org/10.1007/s40120-025-00879-8
