Second Patient Dies Following Treatment With Sarepta’s DMD Gene Therapy Elevidys
In light of the patient’s death, Sarepta put a temporary hold on shipments of Elevidys for patients who are nonambulatory.
A second patient has died following treatment with Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (Elevidys), a marketed adeno-associated virus (AAV) vector-based gene therapy intended to treat Duchenne muscular dystrophy (DMD), according to an announcement from the company.1
The patient was noted to be nonambulatory at the time of treatment and his death was attributed to acute liver failure (ALF).In light of the patient’s death, Sarepta put a temporary hold on shipments of Elevidys for patients who are nonambulatory. Furthermore, the company has voluntarily paused dosing in the phase 3 ENVISION clinical trial (NCT05881408, Study 303), a global study with the role of being the required confirmatory trial for the FDA’s accelerated approval of Elevidys. Sarepta noted that the FDA is aligned on the pausing of dosing in ENVISION and that the company will need the agency’s go-ahead to continue screening and dosing in the study.
Sarepta also stated that in conjunction with a panel composed of clinical experts in multiple disciplines it is working on an enhanced immunosuppressive regimen that includes the use of sirolimus and is intended to bolster the safety of Elevidys for patients who are nonambulatory. According to Sarepta, preclinical research showed that additional immunosuppression was efficacious for moderating liver enzyme elevations. Sarepta is not proposing any changes to the treatment regimen for patients who are ambulatory, which consists of corticosteroid treatment before and after administration of the gene therapy product and monitoring after treatment.
“Our paramount priority is the safety and well-being of the patients we serve,” Louise Rodino-Klapac, PhD, the chief scientific officer and head of research & development at Sarepta, said in a statement.1 “We are taking immediate, decisive steps to better understand and mitigate the risk of acute liver failure, including enhancing the immunosuppressive regimen, for those with Duchenne who are nonambulatory. We are deeply saddened by the loss of a second patient and extend our heartfelt condolences to the patient's family and his care team during this incredibly difficult time. Duchenne muscular dystrophy is a devastating disease that profoundly affects lives and often cuts them far too short. With more than 900 individuals treated to-date, we know how much hope families place in new treatment options like ELEVIDYS – and we are committed to honoring that hope by acting swiftly, guided by scientific rigor and the insights of leading experts, to strengthen safety for all future patients.”
The patient’s death follows that of another patient earlier this year.2 The first patient, whose death was announced in March 2025, was also attributed to ALF following treatment and constituted the first death from ALF after a patient received Elevidys. Notably, this patient was also nonambulatory at the time of treatment.1 Acute liver injury 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
In April 2025, an independent data monitoring committee concluded based on a “totality of evidence” that the risk-benefit-ratio for Elevidys remained favorable for continued dosing in 3 clinical trials without changes to the protocols.3 The finding, shared by Sarepta and its partner Roche, related to 3 clinical trials evaluating Elevidys for which enrollment and dosing were paused in European Union countries at the request of the European Medicines Agency (EMA): the phase 1 Study 104 clinical trial (NCT06241950), the phase 2 ENVOL clinical trial (NCT06128564; Study 302), and ENVISION.3,4
