FDA Restricts Elevidys Use Amidst New Safety Concerns

The FDA has placed Sarepta Therapeutics’ investigational gene therapy clinical trials for Elevidys (delandistrogene moxeparvovec-rokl; Sarepta Therapeutics, Inc) to treat patients with limb muscular dystrophy on clinical hold following 3 deaths that were potentially related to the therapy.¹

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“Protecting patient safety is our highest priority, and the FDA will not allow products whose harms are greater than benefits. The FDA will halt any clinical trial of an investigational product if clinical trial participants would be exposed to an unreasonable and significant risk of illness or injury,” Vinay Prasad, MD, MPH, director of the FDA’s Center for Biologics Evaluation and Research, said in a news release.¹

Following the hold, the company has voluntarily and temporarily paused all shipments of Elevidys in the United States. Since the initial announcement, the FDA recommended the removal of the voluntary hold for ambulatory patients, who may now again receive Elevidys; however, the hold remains for non-ambulatory patients.^1-3

“As a patient-centric organization, the decision to voluntarily and temporarily pause shipments of Elevidys was a painful one, as individuals with Duchenne are losing muscle daily and in need of disease-modifying options,” Doug Ingram, CEO of Sarepta, said in a news release. “It is important for the patients we serve that Sarepta maintains a productive and positive working relationship with the FDA, and it became obvious that maintaining that productive working relationship required this temporary suspension while we address any questions that the FDA may have and complete the Elevidys label supplement process.”²

Elevidys' Indications for Duchenne Muscular Dystrophy

As an adeno-associated virus vector-based gene therapy, Elevidys uses the AAVrh74 Platform Technology from Sarepta Therapeutics for the treatment of Duchenne muscular dystrophy (DMD). The treatment is designed for single intravenous administration. It delivers a gene into the body that prompts the production of micro-dystrophin, a truncated protein weighing 138 kDa.¹

DMD is a rare and serious genetic condition that worsens over time and leads to weakness and deterioration of the body’s muscles. In June 2024, Elevidys received traditional approval for ambulatory DMD in patients aged 4 years and older with a confirmed DMD gene mutation. Previously, in June 2023, Elevidys was approved for non-ambulatory patients through the accelerated approval pathway.¹

Currently, the FDA has informed the company that the indication for Elevidys should be restricted to ambulatory patients only. With the hold announced on July 18, the FDA revoked the AAVrh74 Platform Technology designation because, given new safety information, there is not enough preliminary evidence to show that the AAVrh74 Platform Technology can be used in multiple drugs without causing adverse safety effects. Three fatalities have been observed due to acute liver failure in individuals who received Elevidys or an investigational gene therapy that utilizes the same AAVrh74 serotype. One of these deaths was reported to occur during a clinical trial for limb muscular dystrophy. The FDA is continuing to investigate the product’s safety in ambulatory patients to ensure patient protection.¹

Removal of Hold for Ambulatory Patients

Days after the initial hold, on July 28, the FDA recommended the removal of the voluntary hold for ambulatory patients who now have access to receiving Elevidys. The recommendation follows the investigation of the death of an 8-year-old boy who received Elevidys—ruling his death unrelated to the gene therapy product itself.^3,4

The hold remains for non-ambulatory patients as the FDA continues to work with the company on its safety following the 2 additional deaths.^3,4

“We’ve shown that this FDA takes swift action when patient safety is at risk,” Marty Makary, MD, MPH, FDA commissioner, said in the news release. “We believe in access to drugs for unmet medical needs but are not afraid to take immediate action when a serious safety signal emerges.”¹

REFERENCES
1. FDA Requests Sarepta Therapeutics Suspend Distribution of Elevidys and Places Clinical Trials on Hold for Multiple Gene Therapy Products Following 3 Deaths. FDA. News release. July 18, 2025. Accessed July 29, 2025. https://www.fda.gov/news-events/press-announcements/fda-requests-sarepta-therapeutics-suspend-distribution-elevidys-and-places-clinical-trials-hold

2. Sarepta Therapeutics Announces Voluntary Pause of ELEVIDYS Shipments in the U.S. Sarepta Therapeutics. News release. July 21, 2025. Accessed July 29, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-voluntary-pause-elevidys

3. FDA Recommends Removal of Voluntary Hold for Elevidys for Ambulatory Patients. FDA. News release. July 28, 2025. Accessed July 29, 2025. https://www.fda.gov/news-events/press-announcements/fda-recommends-removal-voluntary-hold-elevidys-ambulatory-patients

4. FDA Investigating Death of 8-Year-Old Boy Who Received Elevidys. FDA. News release. July 25, 2025. Accessed July 29, 2025. https://www.fda.gov/news-events/press-announcements/fda-investigating-death-8-year-old-boy-who-received-elevidys