Independent DMC Concludes that Risk-Benefit Ratio for Sarepta’s DMD Gene Therapy Elevidys Remains Favorable
A recent patient death following treatment with the gene therapy raised concerns for the European Medicines Agency.
An independent data monitoring committee (DMC) concluded based on a “totality of evidence” that the risk-benefit-ratio for Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (marketed as Elevidys), a marketed adeno-associated virus (AAV) vector-based gene therapy intended to treat Duchenne muscular dystrophy (DMD), remains favorable for continued dosing in 3 clinical trials without changes to the protocols.1
The finding, shared by Sarepta and its partner Roche, relates 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 the phase 3 ENVISION clinical trial (NCT05881408, Study 303).1,2 The request was made by the EMA following a March 2025 announcement that a patient identified as a young man had died of acute liver failure (ALF) following treatment with Elevidys in the United States.3 The review of the patient’s case by the DMC was requested by EU reference member authorities.1 Sarepta noted that the analysis was still being finalized as of April 4, 2025, but that it and Roche plan to submit information in response to the trial pauses to EU regulators within a week of that date. EU regulatory process will be followed in the EMA’s assessment of the information and decision on whether to lift the pauses. Sarepta stated that it does not expect that the pauses will have any “material impact” on the timelines for the 3 clinical trials.
“Patient safety and well-being are Roche’s top priority,” Sandra Blum, the global patient partnership leader at Roche, wrote in an March 31, 2025, letter addressed to the World Duchenne Organization.2 “We will be collaborating closely with EMA and sharing updates as we have them. Thank you as always for the role you play in advancing outcomes in Duchenne. We truly appreciate your leadership and the opportunity to work together with you in these efforts.”
The patient’s death was attributed to ALF at the time it was announced, and Sarepta additionally pointed out at the time that the patient had recently experienced a cytomegalovirus (CMV) infection that the investigators noted may have contributed to the patient’s death.3 Acute liver injury is known to be a possible adverse event (AE) associated with AAV vector-based gene therapies such as Elevidys, and is listed as such in the prescribing information for the gene therapy; it thus doesn’t constitute a new safety signal. Although, Sarepta has stated that the prescribing information for Elevidys will be amended to include representation of the patient’s fatal AE.
“Although it is not a new safety signal and the risk/benefit of Elevidys remains positive, ALF leading to death represents a severity of acute liver injury not previously reported for Elevidys, which to date has been used to treat more than 800 clinical and prescribed patients,” the Sarepta Patient Affairs Team wrote in a March 18, 2025, letter addressed to the US Duchenne Community.4 “In addition, testing revealed this patient had a recent CMV infection which was identified by the treating physician as a possible contributing factor. CMV can infect and damage the liver, a condition known as CMV hepatitis.”
