Sarepta’s Duchenne Gene Therapy Trials Paused in Europe Amid Patient Death Investigation

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Key Takeaways

The EMA has requested a temporary hold on studies of Elevidys due to a patient's death from acute liver failure.
Acute liver injury is a known risk of Elevidys, but the severity observed in this case is unprecedented.
The patient had a recent cytomegalovirus infection, potentially contributing to the adverse event.
Sarepta and Roche have paused enrollment and dosing in affected studies, maintaining safety monitoring and data collection.

The European Medicines Agency has requested a pause on 3 clinical trials of FDA-approved gene therapy Elevidys following the death of a patient who suffered acute liver failure after treatment.

According to a recent community letter, the European Medicines Agency (EMA) has requested a temporary clinical hold on Study 104 (NCT06241950), Study 302 (ENVOL, NCT06128564), and Study 303 (ENVISION, NCT05881408) evaluating Sarepta Therapeutics’ Duchenne muscular dystrophy (DMD) gene therapy, delandistrogene moxeparvovec (Elevidys), as regulators investigate the death of a patient who experienced acute liver failure after receiving the therapy.^1,2

In a letter, Sarepta noted that acute liver injury is recognized as a potential adverse effect of the therapy, as well as other AAV-mediated gene therapies, and is included in its prescribing information. Although this is not a new safety concern and the overall risk/benefit profile of the treatment remains favorable, the occurrence of acute liver failure leading to death could represent a severity of liver injury not previously observed with Elevidys, which has been administered to over 800 patients in clinical and prescribed settings.

Additionally, the company noted that testing showed that the patient had a recent cytomegalovirus infection, which the treating physician identified as a possible contributing factor. Sarepta stated in the letter that it prioritizes patient safety and well-being and is continuing to gather and analyze information related to this event. The company noted that the incident has been reported to relevant health authorities, and that it plans to update the prescribing information to accurately reflect this occurrence.

Following the ongoing investigation and analysis of the recent patient death, it may be important to consider the broader context of Elevidys’ clinical trials. Study 104, a phase 1 open-label, systemic gene delivery study sponsored by Sarepta, is focused on evaluating the safety, tolerability, and expression of Elevidys in individuals aged 4 to 9 years who have pre-existing antibodies to recombinant adeno-associated virus serotype rAAVrh74.

Meanwhile, the ENVOL study, sponsored by Roche, is a phase 2 trial that examines the safety and expression of Elevidys micro-dystrophin protein in young children, including infants and newborns. Additionally, the ENVISION study, a global phase 3 trial sponsored by Sarepta, is investigating the safety and efficacy of Elevidys in both ambulatory participants aged 8 to under 18 years and non-ambulatory individuals, with no age limitation.²

In a separate community letter from Roche, the company noted that it is pausing enrollment and dosing of participants in these studies at European country study sites, as well as the United Kingdom for the Roche-sponsored ENVOL study.² It also stated in the letter that patient safety monitoring for already enrolled participants and ongoing collection of data will continue but the community will be collaborating closely with EMA to share updates as they have them.

REFERENCES
1. Community Letter: ELEVIDYS Safety Update. Sarepta Therapeutics. Published March 18, 2025. Accessed April 3, 2025. https://www.sarepta.com/community-letter-elevidys-safety-update
2. Community Letter. Roche. Published March 31, 2025. Accessed April 3, 2024. https://www.duchenneuk.org/wp-content/uploads/2025/04/March-2025-Roche-DMD-Temporary-Clinical-Study-Halt-Community-Letter_31Mar25.pdf