The U.S. Food and Drug Administration (FDA) is reviewing the safety profile of Sarepta Therapeutics’ gene therapy, Elevidys, following the deaths of two non-ambulatory Duchenne muscular dystrophy (DMD) patients. Both patients, teenage boys aged 15 and 16, died from acute liver failure within 90 days of receiving the treatment. The first fatality was reported in March, followed by the second in June.
Elevidys, an adeno-associated virus (AAV) vector-based gene therapy, was initially granted FDA approval in 2024 for ambulatory DMD patients aged four years and above. It remains the only gene therapy approved for Duchenne. Though it was conditionally extended to non-ambulatory patients, it had not met the primary endpoint in a late-stage trial.
The FDA stated in a safety communication on Tuesday that it is “investigating the risk of acute liver failure with serious outcomes, including those such as hospitalization and death, following Elevidys, and is evaluating the need for further regulatory action.” The therapy’s label currently warns of acute liver injury, but not liver failure or fatality. Sarepta reported that it had already proposed an update to the label to reflect the recent incidents.
Both deceased patients had been hospitalized within two months of treatment and were classified as non-ambulatory. One patient weighed 70 kilograms, the other 50 kilograms. These cases led Sarepta to suspend its 2025 sales forecast for Elevidys, pause shipments to non-ambulatory patients, and begin an investigation into the individual and collective circumstances of the two deaths to identify potential common risk factors.
Liver toxicity is a known adverse effect of gene therapies utilizing AAV vectors. In response to the fatalities, Sarepta has indicated its willingness to propose enhanced risk mitigation strategies. This includes the use of sirolimus, an immunosuppressant, specifically to address liver toxicity risks in non-ambulatory patients. The company noted that the FDA had previously inquired whether it had considered additional immunosuppressive measures, including sirolimus.
A full market withdrawal has not been ruled out. There is also a possibility that the use of Elevidys could be restricted solely to ambulatory patients. Additionally, the therapy may receive a black box warning—the most serious type of safety warning in the U.S.—if the agency decides to elevate its current liver toxicity alert.
The ongoing FDA review also arrives during a significant period of transition in the agency’s leadership. The accelerated and subsequent expanded approval of Elevidys had previously stirred internal debate at the FDA. Peter Marks, M.D., Ph.D., the former director of the FDA’s Center for Biologics Evaluation and Research (CBER), had overridden objections from multiple reviewers to approve the therapy. Following Marks’ departure, his successor, Vinay Prasad, M.D., assumed the role in May and has publicly criticized the decision-making around Elevidys.
The U.S. Food and Drug Administration (FDA) has formally opened an investigation into the gene therapy Elevidys — developed by Sarepta Therapeutics for the treatment of Duchenne muscular dystrophy (DMD) — after reports that two non-ambulatory teenage patients died of acute liver failure following administration of the treatment. U.S. Food and Drug Administration+2Fierce Pharma+2
FDA Probes Safety of Elevidys After Fatal Liver Complications in Duchenne Patients
The U.S. Food and Drug Administration (FDA) has launched an investigation into Elevidys, the gene therapy developed by Sarepta Therapeutics for treating Duchenne muscular dystrophy (DMD). The probe follows reports of two non-ambulatory Duchenne patients who died from acute liver failure shortly after receiving Elevidys treatment.
The two fatalities occurred within two months of the single‐infusion therapy being given to patients whose disease had progressed to the point where they could no longer walk. Fierce Pharma+1 While Elevidys’ prescribing documentation already includes a warning about acute serious liver injury, it does not mention liver failure or death explicitly. U.S. Food and Drug Administration
Following the second fatality, Sarepta announced that it would suspend shipments of Elevidys for non-ambulatory patients while an enhanced immunosuppressive regimen is developed and reviewed. Sarepta Investor Relations+2Muscular Dystrophy News+2 The FDA further requested the company to pause clinical trials and considered additional regulatory actions. U.S. Food and Drug Administration
The controversy surrounding Elevidys also raises broader concerns about the balance of risk and benefit in gene therapies for rare diseases. For families of DMD patients, the promise of a one‐time treatment now comes with renewed worry about unforeseen safety issues. STAT+1
According to the FDA, the investigation is ongoing; healthcare providers are urged to closely monitor liver function in patients who have received Elevidys and to report any adverse events. U.S. Food and Drug Administration
