New 3-Year EMBARK Data Highlights Continued Therapeutic Effect of Gene Therapy Elevidys in Duchenne

In recent news, Sarepta revealed new positive findings from its long-term phase 3 EMBARK study (NCT05096221) testing delandistrogene moxeparvovec, or Elevidys, in ambulatory patients with Duchenne muscular dystrophy (DMD). All told, patients from Part 1 of the study on the gene therapy demonstrated notable motor milestone achievements over a 3-year study period, further adding to the drug’s long-term efficacy profile.¹

EMBARK was a double-blind, placebo-controlled, 2-part crossover trial testing a single dose of Elevidys in boys aged 4 to 7 years with DMD. In Part 1, 125 participants were randomized by age and baseline North Star Ambulatory Assessment (NSAA) score to receive Elevidys (1.33 x 1014 vg/kg) or placebo for 52 weeks. In Part 2, groups crossed over, with prior placebo recipients receiving Elevidys and prior Elevidys recipients receiving placebo, each followed for another 52 weeks while maintaining blinding throughout both study phases.

At study initiation, ambulatory participants were 4 to 7 years old; by the final assessment, their mean age was over 9 years. After 3 years of treatment, those who received Elevidys in Part 1 of EMBARK demonstrated a 4.39-point improvement on NSAA, the primary end point, against a pre-specified propensity-weighted untreated external control group (EC). This result, along with other key motor function measures, was statistically significant (P = .0002).

Additional data from the 3-year time point revealed a least square mean (LSM) change of –6.05 seconds (improvement) on Time to Rise (TTR) against EC (P <.0001), as well as a LSM change of –2.70 seconds in 10-meter walk/run (10MWR; P = .0039). At year 3, mean NSAA scores in the Elevidys-treated group (n = 52) remained above baseline, whereas the EC group (n = 73) declined below baseline as expected with age. Furthermore, treatment with Elevidys in these patients was associated with 73% and 70% slowing of disease progression as measured by TTR and 10MWR, respectively.

“As a pediatric neurologist, I spend time with families who are doing everything they can to help their children stay strong in the face of Duchenne,” Crystal Proud, MD, chief of neurology and director of Neuromuscular Medicine at Children’s Hospital of The King’s Daughters, said in a statement.¹ “The EMBARK results give us a clearer picture of how treatment with ELEVIDYS can make a meaningful difference over time, and they reflect what I see in clinical practice – helping boys perform everyday movements, such as standing, walking and running with greater strength and speed than what we expect as Duchenne progresses without a disease-modifying treatment.”

EMBARK, which has had data readout each of the last few years, serves as a post-marketing trial to further confirm Elevidy’s efficacy and safety as a treatment for the DMD community. Elevidys, an adeno-associated vector-based gene therapy, gained FDA-approved under the accelerated approval pathway in June 2023. Nearly a year later, the therapy received traditional approval for ambulatory patients with DMD and an expanded label for those aged 4 years and older, while also gaining accelerated approval for nonambulatory patients pending confirmation of clinical benefit in a follow-up trial.^2,3

According to Sarepta, there were no new treatment-related safety signals observed in the 3-year findings.¹ Over the past year, the safety of the treatment has come under question, with 2 fatal cases of acute liver failure in nonambulatory pediatric boys reported in June 2025. Following these events, Sarepta voluntarily paused the distribution of the gene therapy to nonambulatory patients to get a better handle of the safety concerns.^4,5

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After completing a comprehensive review of available safety data, the FDA approved several substantial revisions to the drug’s labeling in November 2025. These updates added a boxed warning describing the risk of serious liver injury and acute liver failure, including fatal cases, and revised the indication to limit use to ambulatory patients aged 4 years and older with DMD and a confirmed gene mutation.

The agency removed the indication for nonambulatory patients and added a limitations of use statement to guide clinical decision-making, along with revisions across multiple sections of the prescribing information, including warnings and precautions, dosing and administration, adverse reactions, use in specific populations, clinical studies, and patient counseling. The updated labeling also includes a new medication guide for patients and caregivers.

The revised labeling for delandistrogene moxeparvovec-rokl further introduced enhanced safety and monitoring recommendations, advising weekly liver function testing for at least 3 months post-treatment and for patients to remain near an appropriate medical facility for 2 months after infusion. Patients are also instructed to seek prompt medical attention if they develop jaundice, miss or vomit corticosteroid doses, or experience changes in mental status.

Two-year findings from EMBARK were previously released around this time last year, and later published in Neurology & Therapy. At the 2-year mark, compared with EC, ELEVIDYS was associated with a 2.34-point improvement from baseline in NSAA at 52 weeks (P < .0001). Despite being older on average, patients in the crossover group (n = 59) also demonstrated clinically meaningful and statistically significant improvements in NSAA, TTR (–2.70 seconds; P < .0001), and 10MWR (–1.07 seconds; P = .0001).⁶

Between week 52 and week 104, there were no new safety signals that emerged. From baseline to week 104, investigators reported no treatment-related deaths, study discontinuations because of adverse events, or clinically significant complement-mediated adverse events.

REFERENCES
1. Sarepta Announces Positive Topline Three-Year EMBARK Results Showing ELEVIDYS Significantly Slows Disease Progression on Key Functional Measures in Ambulatory Duchenne Patients. News release. Sarepta Therapeutics. January 26, 2026. Accessed January 28, 2026. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-announces-positive-topline-three-year-embark-results
2. Sarepta Therapeutics announces FDA approval of Elevidys, the first gene therapy to treat Duchenne muscular dystrophy. News release. June 22, 2023. Accessed January 28, 2026. https://www.businesswire.com/news/home/20230622454844/en/
3. Sarepta Therapeutics Announces Expanded US FDA Approval of ELEVIDYS to Duchenne Muscular Dystrophy Patients Ages 4 and Above. News Release. Sarepta Therapeutics. Published June 20, 2024. Accessed January 28, 2026. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-expanded-us-fda-approval-elevidys?_ga=2.261745871.332981042.1718920455-330115727.1718920455
4. FDA Approves New Safety Warning and Revised Indication that Limits Use for Elevidys Following Reports of Fatal Liver Injury. News release. U.S. Food and Drug Administration. November 14, 2025. Accessed January 28, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-new-safety-warning-and-revised-indication-limits-use-elevidys-following-reports-fatal?utm_medium=email&utm_source=govdelivery
5. FDA Requests Sarepta Therapeutics Suspend Distribution of Elevidys and Places Clinical Trials on Hold for Multiple Gene Therapy Products Following 3 Deaths. News release. FDA. July 18, 2025. Accessed January 28, 2026. https://www.fda.gov/news-events/press-announcements/fda-requests-sarepta-therapeutics-suspend-distribution-elevidys-and-places-clinical-trials-hold
6. Sarepta Therapeutics Announces Results from Part 2 of the EMBARK Study Demonstrating Sustained Benefits and Disease Stabilization in Ambulatory Individuals with Duchenne Muscular Dystrophy Following Treatment with ELEVIDYS. News release. Sarepta. January 27, 2025. Accessed January 28, 2026. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-results-part-2-embark-study