FDA Shuts Down Sarepta's Distribution of Gene Therapy Elevidys Following Patient Deaths

Marty Makary, MD, MPH

This article was originally published and updated to include relevant information.

Following the reported deaths of 3 patients, the FDA has requested Sarepta Therapeutics' to suspend the distribution of Elevidys, its approved gene therapy for Duchenne muscular dystrophy (DMD), as well as pause clinical trials testing the company's gene therapy agents.¹

The latest death, a 51-year-old man with limb-girdle muscular dystrophy (LGMD) type 2D/R3, was enrolled in the company’s phase 1 study testing SRP-9004, also known as patidistrogene bexoparvovec. According to several reports, this incidence occurred last month and was caused by liver failure, the same reason for the two previously reported deaths.^2,3

According to the announcement, the FDA revoked Sarepta’s platform technology designation and met with the company to request a voluntary halt on all Elevidys shipments. Sarepta declined to comply with the agency’s request. The reasons for revoking were because of insufficient evidence—especially in light of new safety concerns—that the company's AAVrh74 Platform Technology can be used across multiple drugs without compromising safety.

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

For now, the agency is taking precaution, trying to understand whether the incidents that occurred were related to these products and to avoid future unreasonable illness or injury.

"Protecting patient safety is our highest priority, and the FDA will not allow products whose harms are greater than benefits," Vinay Prasad, MD, MPH, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement.¹ "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."

Last month, Roche announced new dosing restrictions for Elevidys, limiting its use in non-ambulatory patients with DMD, irrespective of age, in both clinical and commercial settings. At the time, the company noted that non-ambulatory patients in commercial settings would no longer receive the gene therapy, while enrollment and dosing of non-ambulatory patients in trial settings would be immediately paused until risk mitigation measures were implemented in the study protocol.^3,4

The decision came after the assessment of the 2 original patient deaths, both of whom were non-ambulatory, and died of fatal acute liver failure. In the announcement, the company noted that the dosing restrictions would not impact ambulatory patients with DMD. Elevidys, which received traditional approval in 2024 for ambulatory patients with DMD, is the first and only marketed gene therapy specific to patients with DMD, a disease that affects approximately 20,000 individuals in the United States.

Levi Garraway, MD, PhD

In addition to suspending shipments of Elevidys for non-ambulatory patients, Sarepta voluntarily paused dosing in the phase 3 ENVISION clinical trial, a placebo-controlled study testing the gene therapy in older ambulatory and non-ambulatory patients with DMD. This decision, aligned with the FDA, was done to allow for more evaluation of a protocol amendment that incorporated an enhanced immunosuppressive regimen of sirolimus for the non-ambulatory patient cohort. For context, ENVISION serves as a confirmatory trial required under the FDA’s accelerated approval pathway for non-ambulatory patients.

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"We are deeply saddened by the loss of these two young men and are urgently working to mitigate any risks related to the use of Elevidys,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, said in a statement at the time.³ “Patient safety is always our highest priority. Therefore, we have recommended halting treatment with Elevidys in non-ambulatory patients with immediate effect.”

Following the first case of fatal acute liver failure, European regulators requested that Roche and Sarepta put temporary clinical holds in other studies, such as 104 (NCT0624195) and 302 (ENVOL; NCT06128564), in addition to ENVISION. Roche noted that the temporary clinical holds are still in effect, and that dosing will be paused immediately.

A month after companies provided a safety update for Elevidys, Sarepta announced the FDA requested that the label for Elevidys be changed to include a black box warning for acute liver injury and acute liver failure. In response, Sarepta convened an expert committee of neuromuscular specialists, hepatologists, hematologists, and immunologists to review these patient cases, with findings that are expected to be presented to the FDA.⁵

Sarepta announced several other notable updates as well, including slashing 36% of its workforce, impacting approximately 500 employees, to save $400 million annually. The company plans to reprioritize its clinical pipeline, shifting gears to more potentially best-in-class siRNA platform assets. In addition, Sarepta plans to discuss a proposal with the FDA to gather data on the regimen in a new cohort (Cohort 8) of the ENDEAVOR study as a pathway to re-establish dosing in the non-ambulatory setting.

Elevidys, also known as SRP-9001, is an AAV vector-based therapy that was originally approved under the accelerated approval pathway in June 2023 for ambulatory patients with DMD. Less than a year after its original approval, the agent gained traditional approval for this same patient population, while receiving accelerated approval for non-ambulatory patients, with continued approval contingent upon verification of clinical benefit in a confirmatory trial.⁶

REFERENCES
1. FDA Requests Sarepta Therapeutics Suspend Distribution of Elevidys and Places Clinical Trials on Hold for Multiple Gene Therapy Products Following 3 Deaths. News release. FDA. July 18, 2025. Accessed July 18, 2025. https://www.fda.gov/news-events/press-announcements/fda-requests-sarepta-therapeutics-suspend-distribution-elevidys-and-places-clinical-trials-hold
2. UPDATED: Analysts demand transparency after Sarepta's roundabout disclosure of 3rd patient death. Fierce Biotech. July 18, 2025. Accessed July 18, 2025. https://www.fiercebiotech.com/biotech/3rd-patient-dies-following-treatment-sarepta-gene-therapy-reports
3. Sarepta Therapeutics Crashes After A Third Gene Therapy Patient Dies. Investor’s Business Daily. July 18, 2025. Accessed July 18, 2025. https://www.investors.com/news/technology/sarepta-stock-patient-death-gene-therapy-restructuring/
4. [Ad hoc announcement pursuant to Art. 53 LR] Roche provides safety update on Elevidys™ gene therapy for Duchenne muscular dystrophy in non-ambulatory patients. Roche. June 15, 2025. Accessed July 18, 2025. https://www.globenewswire.com/news-release/2025/06/15/3099406/0/en/Ad-hoc-announcement-pursuant-to-Art-53-LR-Roche-provides-safety-update-on-Elevidys-gene-therapy-for-Duchenne-muscular-dystrophy-in-non-ambulatory-patients.html
5. Sarepta Provides Safety Update for ELEVIDYS and Initiates Steps to Strengthen Safety in Non-Ambulatory Individuals with Duchenne. June 15, 2025. Accessed July 18, 2025. https://www.businesswire.com/news/home/20250614701775/en/Sarepta-Provides-Safety-Update-for-ELEVIDYS-and-Initiates-Steps-to-Strengthen-Safety-in-Non-Ambulatory-Individuals-with-Duchenne
6. Sarepta Therapeutics Announces Strategic Restructuring and Pipeline Prioritization Plan to Maintain Long-term, Sustainable Growth and Provides Update on ELEVIDYS Label. News release. Sarepta Therapeutics. July 16, 2025. Accessed July 18, 2025.
7. Sarepta Therapeutics Announces Expanded US FDA Approval of ELEVIDYS to Duchenne Muscular Dystrophy Patients Ages 4 and Above. News Release. Sarepta Therapeutics. Published June 20, 2024. Accessed July 18, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-expanded-us-fda-approval-elevidys?_ga=2.261745871.332981042.1718920455-330115727.1718920455