DMD Gene Therapy Shows Efficacy, Safety in Patients Treated at 2 Years Old

Study participants with Duchenne muscular dystrophy (DMD) who were 2 years old at the time of treatment with delandistrogene moxeparvovec (Elevidys; Sarepta Therapeutics) showed promising biomarker results and no new safety signals, according to a press release from Sarepta.1

Based on western blot testing, patients who received gene therapy at 2 years old showed a mean dystrophin expression of 93.87% of normal. | Image Credit: Treecha - stock.adobe.com

The new results come from Study 9001-103, also known as the ENDEAVOR trial (NCT04626674), a multicohort study evaluating dystrophin expression and safety after delandistrogene moxeparvovec treatment in patients with DMD.2 Participants in cohort 6 of the trial who were 2 years old at the time of treatment (n = 6) were included in the new analysis.1

Based on western blot testing, these patients showed a mean dystrophin expression of 93.87% of normal. Immunofluorescence showed 79.9% dystrophin-positive fibers, with results seen in biopsies from 12 weeks after treatment. Previous results from cohort 4 of the study, which included patients aged 3 years at the time of treatment (n = 7), showed mean dystrophin protein levels of 99.64% based on western blot testing at 12 weeks post treatment, according to the press release.

The main end point in ENDEAVOR is the change from baseline in the quantity of micro-dystrophin protein expression based on western blot; the change from baseline in micro-dystrophin expression based on the percent dystrophin-positive fibers at 12 weeks is a secondary outcome. The change in vector genome copies per nucleus, North Star Ambulatory Assessment scores, and certain timed functional tests are among exploratory end points.

The ENDEAVOR study has enrolled 55 patients with DMD in 7 cohorts and has dosed patients younger than 4 years, aged 4 to 7 years, and both ambulatory and nonambulatory older patients. Participants are followed for 5 years, including the initial 12-week period.

“The strength of the biomarker results that we are seeing in younger patients is extremely encouraging and we have a meeting with US FDA next month to discuss expanding the Elevidys label to include younger patients,” Louise Rodino-Klapac, PhD, chief scientific officer and head of research and development, Sarepta Therapeutics, said in a press release. “In addition to positive expression results, the safety profile in these patients is consistent with what we’ve seen in prior studies and in patients who have been prescribed treatment.”

The safety profile of delandistrogene moxeparvovec among patients in cohort 6 was consistent with clinical and real-world experience. Nausea and vomiting were the most common adverse events, and 2 patients experienced elevated liver enzymes that resolved with steroid treatment.

Real-world data presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference in March demonstrated signs of efficacy and a tolerable safety profile with delandistrogene moxeparvovec, adding to the understanding of the therapy’s efficacy outside of clinical trials.3 Additional findings indicated that the cardiac safety profile of delandistrogene moxeparvovec is manageable, with no signs of persistent cardiac injury related to the gene therapy.

Delandistrogene moxeparvovec is an adeno-associated virus vector-based treatment that was initially FDA approved in June 2023 for patients with DMD aged 4 to 5 years and received expanded approval in June 2024 for the treatment of all patients aged 4 years and older. In nonambulatory patients, the gene therapy’s approval is under the FDA’s accelerated approval pathway.4 The therapy is contraindicated in patients with deletion in exon 8 and/or exon 9 in the DMD gene.1

References

1. Sarepta Therapeutics shares new protein expression and safety results from ENDEAVOR in participants 2 years old at time of treatment. News release. Sarepta Therapeutics. May 16, 2025. Accessed May 23, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-shares-new-protein-expression-and-safety

2. A gene transfer therapy study to evaluate the safety of and expression from delandistrogene moxeparvovec (SRP-9001) in participants with Duchenne muscular dystrophy (DMD) (ENDEAVOR). ClinicalTrials.gov. Updated August 26, 2024. Accessed May 23, 2025. https://clinicaltrials.gov/study/NCT04626674

3. McNulty R. Real-world study suggests DMD gene therapy is safe, effective. AJMC®. March 26, 2025. Accessed May 23, 2025. https://www.ajmc.com/view/real-world-study-suggests-dmd-gene-therapy-is-safe-effective

4. Shaw M. FDA grants 2 approvals to delandistrogene moxeparvovec for DMD. AJMC. June 20, 2024. Accessed May 23, 2025. https://www.ajmc.com/view/fda-grants-2-approvals-to-delandistrogene-moxeparvovec-for-dmd