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.
In a social media post in March, Prasad wrote that Marks “[o]verturned 3 reviewers to approve a [Duchenne] gene therapy that seems to be killing children and blowing their livers up.” Prasad has since voiced intentions to maintain regulatory flexibility, particularly regarding therapies targeting pediatric and rare conditions.
Leadership changes within CBER have continued, with the departures of Nicole Verdun and Rachael Anatol, Ph.D., who oversaw the FDA’s gene and cell therapy division.
