European Medicines Agency Requests Pause on Trials for Sarepta’s DMD Gene Therapy Elevidys

The European Medicines Agency (EMA) has requested a temporary pause on 3 clinical trials evaluating Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (marketed as Elevidys), an adeno-associated virus (AAV) vector-based gene therapy intended to treat Duchenne muscular dystrophy (DMD), in Europe.¹

Sarepta partner Roche, which revealed the news in a letter addressed to the World Duchenne Organization, stated that the companies are complying with the request, and that enrollment and dosing have been paused for European Union country sites in the trials. The 3 trials include the phase 1 Study 104 clinical trial (NCT06241950), the phase 2 ENVOL clinical trial (NCT06128564; Study 302), and the phase 3 ENVISION clinical trial (NCT05881408, Study 303). Roche noted that for ENVOL, the pause would be applied at sites in the United Kingdom, as well. Safety monitoring and data collection for patients that have already been enrolled will continue at all sites.

The move comes after an announcement made on March 18, 2025, that a patient, identified as a young man, who had been treated with Elevidys in the United States, had died.² Although the patient’s death was attributed to acute liver failure (ALF) at that time of the announcement, Roche noted in the letter regarding the trial pauses that assessment and analysis of data regarding the patient’s death is still ongoing.^1,2

“Patient safety and well-being are Roche’s top priority,” Sandra Blum, the global patient partnership leader at Roche, wrote in the letter.¹ “We will be collaborating closely with EMA and sharing updates as we have them. Thank you as always for the role you play in advancing outcomes in Duchenne. We truly appreciate your leadership and the opportunity to work together with you in these efforts.”

ALF is known to be a possible adverse event associated with AAV vector-based gene therapies such as Elevidys, and is listed as such in the prescribing information for the gene therapy.² Although, Sarepta noted that following the patient’s death, the prescribing information for Elevidys will be amended to include representation of this event.

Long-term safety data from pooled results from clinical trial evaluating Elevidys were recently presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 16-19 in Dallas, Texas.³ The pooled analysis included 156 patients, with up to 5 years of fllow-up, treated across 4 clinical trials, including Study 101 (NCT03375164), Study 102 (NCT03769116), ENDEAVOR Cohorts 1-5b (NCT04626674), and EMBARK Part 1 (NCT05096221). As of January 15, 2024, no deaths or study discontinuations had been reported. The overall safety and tolerability profile of the gene therapy product was deemed manageable, regardless of age, weight, or disease stage, and the most common treatment-related, treatment-emergent adverse events were vomiting, nausea, decreased appetite, increased glutamate dehydrogenase levels, and upper abdominal pain.

REFERENCES
1. Letter addressed to members of the World Duchenne Organization. Letter. Sarepta Therapeutics. March 31, 2025. Accessed April 3, 2025. https://www.duchenneuk.org/wp-content/uploads/2025/04/March-2025-Roche-DMD-Temporary-Clinical-Study-Halt-Community-Letter_31Mar25.pdf
2. Sarepta Therapeutics shares safety update on Elevidys. News release. Sarepta Therapeutics, Inc. March 18, 2025. Accessed April 3, 2025. https://investorrelations.sarepta.com/static-files/0d505d91-6722-4528-aae0-1e99fcbc37e5
3. Mendell J. Long-Term Safety and Tolerability of DelandistrogeneMoxeparvovec in Duchenne Muscular Dystrophy: Phase 1 to Phase 3 Clinical Trials. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-19. Dallas, TX. Abstract P89.