Medically Written and Reviewed By:
Vikas Londhe, MPharm
On June 15, 2025, Sarepta Therapeutics announced the second death of a teenage male patient linked to acute liver failure (ALF) following its one-time gene therapy drug Elevidys in a non ambulatory Duchenne Muscular Dystrophy (DMD) patient, someone who is no longer able to walk due to this condition. The first fatality occurred in March 2025, when a 16-year-old boy succumbed to liver failure months after his treatment with Elevidys.
Official response
As soon as Sarepta was aware about adverse event, they suspended all commercial shipments of Elevidys to non‑ambulatory patients. Sarepta has completely paused dosing to non-ambulatory patient cohort in ENVISION Phase III trial which is going on in ambulatory and non-ambulatory older patient globally; as they are focusing on designing and enhancing more acceptable immunosuppressant regimen along with Elevidys.
Sarepta summon an independent panel of DMD and liver experts to evaluate alternate therapies like sirolimus in combination with corticosteroids to mitigate liver failure risk.
Alongside, Sarepta is continuously discussing with the FDA and other regulatory bodies their proposed plan for this event.
Roche, which is partnered with Sarepta and is responsible for Elevidys’ marketing outside the United States, has equally halted dosing and shipments of Elevidys for non‑ambulatory patients globally.
Sarepta has particularly reported that both fatalities were associated with non-ambulatory patients who were no longer able to walk, a subgroup with advanced DMD. Approximately 140 such patients have been treated, and now, with two ALF-related deaths, this is considered to be a serious safety signal.
However ambulatory patients (those still walking) can continue treatment under the current corticosteroid regimen, as company has not amended protocols for them.
Elevidys & liver risk
Elevidys (delandistrogene moxeparvovec) is an innovative gene therapy that uses an Adeno-Associated Virus (AAV) as a delivery system to transport a micro‑dystrophin genetic material into the body via a single IV infusion. AAV-based gene therapies are known to cause acute liver injury, which can lead to liver failure, though fatalities were rare.
The Elevidys’ previous FDA approval already requires corticosteroid administration one day before initiating treatment and continuing for 60 days post-administration, along with close monitoring for liver function, but those measures have not prevented these rare, severe outcomes. Sarepta is now working on an enhanced safety regimen, which may include the addition of the extra immunosuppressant drug sirolimus into the current corticosteroid regimen. This modification of treatment is held up by preclinical data, which demonstrated sirolimus’ effectiveness in suppressing certain liver enzymes, which may help to mitigate this potential safety signal.
Implications for patients and the market
The tragic loss of two non-ambulatory patients highlights the importance of carefully analyzing Elevidys’s further benefits against the serious risks of liver failure in this subgroup. The ENVISION trial will be amended to include stronger immunosuppressant protocols by the addition of sirolimus; however, this change must receive FDA clearance before dosing resumes. While the FDA has agreed to the pause and is reviewing emerging safety data, full restoration of the trial and treatment depends on how effectively Sarepta is mitigating liver risk in non-ambulatory patient populations.
Summary
Sarepta Therapeutics has reported a second death from acute liver failure in a non-ambulatory patient treated with its Duchenne Muscular Dystrophy gene therapy, Elevidys. Both fatalities occurred in patients who were no longer able to walk, prompting Sarepta and its partner Roche to suspend dosing and commercial shipments of Elevidys for this subgroup globally; however, treatment continues for ambulatory patients. For the time being, dosing to the non-ambulatory cohort group in the Phase III ENVISION trial is on hold pending regulatory review of enhanced immunosuppressant protocols, possibly for the addition of sirolimus into the regimen. The company is working with an independent panel of experts to evaluate stronger liver-protection strategies. These developments have deepened inspection of Elevidys’s safety profile, particularly in advanced-stage DMD. At the same time, it is raising questions about gene therapy risks.
References
Sarepta Community Letter: Safety Update regarding Elevidys in non-ambulatory individuals with Duchenne, Sarepta Therapeutics, June 15, 2025, https://www.parentprojectmd.org/wp-content/uploads/2025/06/Elevidys-Community-Letter-6.15.2025.pdf
Highlights of prescribing information, Elevidys, https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert-ELEVIDYS_1.pdf
Sarepta Reports Second Death of Patient Using Its Gene Therapy, Bloomberg, https://www.bloomberg.com/news/articles/2025-06-15/sarepta-reports-second-death-of-patient-using-its-gene-therapy
Sarepta reports second case of liver failure death after its gene therapy treatment, Reuters, https://www.reuters.com/business/healthcare-pharmaceuticals/sarepta-reports-second-case-liver-failure-death-after-its-gene-therapy-treatment-2025-06-15/
A safety update on Elevidys, June-2025, Parent Project Muscular Dystrophy, https://www.parentprojectmd.org/a-safety-update-on-elevidys-june-2025/?utm_source=chatgpt.com
Second DMD Patient Dies after Treatment with Sarepta Gene Therapy, https://www.genengnews.com/topics/genome-editing/second-dmd-patient-dies-after-treatment-with-sarepta-gene-therapy/
Sarepta Provides Safety Update for ELEVIDYS and Initiates Steps to Strengthen Safety in Non-Ambulatory Individuals with Duchenne, Sarepta Therapeutics, https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-provides-safety-update-elevidys-and-initiates-steps
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