Since March 2025, there have been two reported deaths following treatment with ELEVIDYS. Both patients were non-ambulatory, ages 16 and 15 and both died related to acute liver failure.
ELEVIDYS is the only FDA approved gene therapy for patients with Duchenne Muscular Dystrophy (DMD). It was first approved on June 22, 2023, for the treatment of ambulatory pediatric patients aged 4 through 5 years with confirmed DMD gene mutation but excluded those with deletions in exon 8 and/or exon 9. On June 20, 2024, the FDA expanded the indication to include patients over the age of 4 years, ambulatory and non-ambulatory, with confirmed DMD gene mutation, but excluded those with deletions in exon 8 and/or exon 9. Worldwide, ELEVIDYS has been given to more than 900 individuals.
Following the second death, Sarepta issued press release on June 15, 2025, titled “Sarepta Provides Safety Update for ELEVIDYS and Initiates Steps to Strengthen Safety in Non-Ambulatory Individuals with Duchenne.” As it examines the data, the company has initiated several safety initiatives as noted in the following excerpts from the press release.
Evaluating and Enhancing Immunosuppressive Regimen: As part of a comprehensive review of safety data, Sarepta is taking proactive steps to mitigate the risk of acute liver failure in non-ambulatory patients. Sarepta is working to immediately convene an independent group of leading experts in Duchenne and liver health to consider an enhanced immunosuppression regimen for ELEVIDYS. This panel will evaluate data and assess our proposed regimen, which includes sirolimus and is supported by preclinical data demonstrating the effectiveness of additional immunosuppression in moderating liver enzyme elevations, a key factor in mitigating potential safety events. Sarepta will share the panel's recommendations with the U.S. Food & Drug Administration (FDA), and implementation of any new regimen will be subject to FDA guidance and allowance.
Suspending Shipments of ELEVIDYS for Non-Ambulatory Patients: Sarepta is temporarily suspending shipments of ELEVIDYS for non-ambulatory patients while an enhanced immunosuppressive regimen is evaluated, discussed with regulatory bodies, and put in place.
For ambulatory patients, no treatment changes are being proposed and the current practice of administering corticosteroids before and after ELEVIDYS infusion, along with post-treatment monitoring, remains the same.
ENVISION Study Paused: Sarepta has voluntarily paused dosing in the ENVISION clinical study (also known as Study SRP-9001-303). FDA concurs with this action. The pause will allow for the evaluation of a protocol amendment to incorporate an enhanced immunosuppressive regimen for the non-ambulatory patient cohort and incorporate any additional feedback from the FDA. Regulatory alignment is needed before screening and dosing in ENVISION may resume.
ENVISION is a global, randomized, double-blind, placebo-controlled trial evaluating ELEVIDYS in older ambulatory and non-ambulatory individuals living with Duchenne muscular dystrophy. In the U.S., it serves as the confirmatory trial required under the FDA’s accelerated approval pathway for non-ambulatory patients.
Although gene therapies like ELEVIDYS offer an opportunity to address the underlying genetic cause rather than just managing symptoms for diseases with few alternatives, the benefit is not without risk. Severe immune system response is a known risk and continues to be a challenge for gene therapies that use adeno-associated viral vectors.
Article by Kathy Clark, RN, BSN, CMCN, RIT, Vice President, Director of Managed Care. For more information about how this may affect your plan, please contact your Summit ReSources care specialist. The following sources were used as reference material for this article:
(1) Sarepta Provides Safety Update for ELEVIDYS and Initiates Steps to Strengthen Safety in Non-Ambulatory Individuals with Duchenne https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-provides-safety-update-ELEVIDYS-and-initiates-steps?_ga=2.137210743.63220694.1750092019-638846657.1750092019 Accessed 6/16/2025.
(2) Bilodeau, K. March 21, 2025. A recent gene therapy death shines a light on AAV safety. PharmaVoice. https://www.pharmavoice.com/news/sarepta-ELEVIDYS-gene-therapy-duchenne-death-aav-safety/743824/ Accessed 6/16/2025.