Other safety alerts
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| The United States: FDA Requests Sarepta Therapeutics Suspend Distribution of Elevidys and Places Clinical Trials on Hold for Multiple Gene Therapy Products Following 3 Deaths |
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The United States (U.S.) Food and Drug Administration (FDA) announces that it has placed Sarepta Therapeutics investigational gene therapy clinical trials for limb girdle muscular dystrophy on clinical hold following three deaths potentially related to these products and new safety concerns that the study participants are or would be exposed to an unreasonable and significant risk of illness or injury. The FDA has also revoked Sarepta’s platform technology designation.
The FDA leadership also met with Sarepta Therapeutics and requested it voluntarily stop all shipments of Elevidys today. The company refused to do so.
As of July 18, 2025, the FDA has received three reports of fatal acute liver failure following treatment of patients with Sarepta AAVrh74 gene therapies that appear to have been caused by the gene therapy products as a result of acute liver failure.
The three deaths appear to have been a result of acute liver failure in individuals treated with Elevidys or investigational gene therapy using the same AAVrh74 serotype that is used in Elevidys. One of the fatalities occurred during a clinical trial conducted under an investigational new drug application for the treatment of Limb Girdle Muscular Dystrophy.
Two of these deaths were reported in non-ambulatory pediatric male patients with Duchenne Muscular Dystrophy (DMD) following treatment with ELEVIDYS (delandistrogene moxeparvovec-rokl), and previously described in June 24, 2025 communication: FDA Investigating Deaths Due to Acute Liver Failure in Non-ambulatory Duchenne Muscular Dystrophy Patients Following ELEVIDYS. Elevidys is an AAVrh74 adeno-associated virus vector-based gene therapy.
A third death was reported in an adult male patient with Limb Girdle Muscular Dystrophy following treatment with a Sarepta AAVrh74 gene therapy product in a clinical trial, who presented with abnormal liver function tests. This patient presented with elevated transaminases and was hospitalized less than two months after treatment with the investigational gene therapy product. The patient progressed to liver failure and died 80 days after he received the investigational gene therapy.
Elevidys is an adeno-associated virus vector-based gene therapy using Sarepta Therapeutics, Inc.’s AAVrh74 Platform Technology for the treatment of DMD. It is designed to deliver into the body a gene that leads to production of Elevidys micro-dystrophin, a shortened protein (138 kDa, compared to the 427 kDa dystrophin protein of normal muscle cells) that contains selected domains of the dystrophin protein present in normal muscle cells. The product is administered as a single intravenous dose.
DMD is a rare and serious genetic condition which worsens over time, leading to weakness and wasting away of the body’s muscles. The disease occurs due to a defective gene that results in abnormalities in, or absence of, dystrophin, a protein that helps keep the body’s muscle cells intact.
The FDA revoked the platform technology designation for Sarepta’s AAVrh74 Platform Technology because, among other things, given the new safety information, the preliminary evidence is insufficient to demonstrate that AAVrh74 Platform Technology has the potential to be incorporated in, or utilized by, more than one drug without an adverse effect on safety.
In the U.S., Elevidys received traditional approval for use in ambulatory DMD patients 4 years of age and older with a confirmed mutation in the DMD gene on June 20, 2024. It was approved for non-ambulatory patients on June 22, 2023 under the accelerated approval pathway. This pathway can allow earlier approval based on an effect on a surrogate endpoint or intermediate clinical endpoint that is reasonably likely to predict clinical benefit, while the company conducts confirmatory studies to verify the predicted clinical benefit. Continued approval for non-ambulatory patients is contingent upon verification and description of clinical benefit in a confirmatory trial. Given the new safety information, the FDA has notified the company that the indication should be restricted to use in ambulatory patients. The FDA is committed to further investigating the safety of the product in ambulatory patients and will take additional steps to protect patients as needed.
The FDA is continuing to investigate the risk of acute liver failure with serious outcomes, including those such as hospitalization and death, following gene therapies using Sarepta’s AAVrh74 Platform Technology, and the need for further regulatory actions.
Please refer to the following websites in FDA for details:
http://www.fda.gov/news-events/press-announcements/fda-requests-sarepta-therapeutics-suspend-distribution-elevidys-and-places-clinical-trials-hold ; and
http://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-deaths-due-acute-liver-failure-following-treatment-sareptas-aavrh74-gene-therapies
In Hong Kong, the above products are not registered pharmaceutical products. Related news were previously issued by Singapore Health Sciences Authority and the FDA, and were posted on the Drug Office website on 25 Mar 2025, 24 Jun 2025 and 25 Jun 2025.
Ends/Saturday, Jul 19, 2025
Issued at HKT 12:00
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