FDA Places Sarepta Therapeutics Gene Therapy Trials on Hold, Requests Suspend Distribution of Elevidys Following 3 Deaths.

The FDA has placed Sarepta Therapeutics' clinical trials for limb girdle muscular dystrophy on hold following three deaths potentially related to the products. The FDA has also revoked Sarepta's platform technology designation and requested the company stop all shipments of Elevidys, which it refused to do. The deaths appear to be a result of acute liver failure in individuals treated with Elevidys or a similar gene therapy product. The FDA prioritizes patient safety and will halt any clinical trial if participants are exposed to an unreasonable risk of illness or injury.

The U.S. Food and Drug Administration (FDA) has placed Sarepta Therapeutics' clinical trials for limb girdle muscular dystrophy on hold following three deaths potentially related to the products. The FDA has also revoked Sarepta's platform technology designation and requested the company stop all shipments of Elevidys, which it refused to do. The deaths appear to be a result of acute liver failure in individuals treated with Elevidys or a similar gene therapy product. The FDA prioritizes patient safety and will halt any clinical trial if participants are exposed to an unreasonable risk of illness or injury.

The FDA announced that it had placed Sarepta's investigational gene therapy clinical trials 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 [1].

Elevidys is an adeno-associated virus vector-based gene therapy using Sarepta's AAVrh74 Platform Technology for the treatment of Duchenne muscular dystrophy (DMD). It is designed to deliver into the body a gene that leads to production of micro-dystrophin, a shortened protein that contains selected domains of the dystrophin protein present in normal muscle cells. The product is administered as a single intravenous dose [1].

The FDA leadership met with Sarepta Therapeutics and requested it voluntarily stop all shipments of Elevidys today. The company refused to do so. "Today, we’ve shown that this FDA takes swift action when patient safety is at risk," said FDA Commissioner Marty Makary, M.D., M.P.H. "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].

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 [1].

Another person treated with a Sarepta Therapeutics gene therapy has died, compounding concerns about the safety of the company’s genetic treatments. Sarepta on Friday confirmed the death of a 51-year-old patient with limb-girdle muscular dystrophy who died after treatment with the company’s experimental SRP-9004 therapy in a Phase 1 study [2].

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 has notified the company that the indication should be restricted to use in ambulatory patients [1].

The FDA's actions follow the recent deaths of two teenagers with Duchenne muscular dystrophy who received Sarepta's marketed gene therapy Elevidys. The two deaths were the first reported among more than 900 people who had been treated with it in clinical testing and commercially as of June [2].

The company is working on a regimen of immune-suppressing drugs to help manage the safety risks in older Duchenne patients who can still walk, and plans to soon share its findings with the FDA. In the meantime, the agency placed a “black box” safety warning on Elevidys’ label for the risk of liver failure [2].

References:
[1] https://www.fda.gov/news-events/press-announcements/fda-requests-sarepta-therapeutics-suspend-distribution-elevidys-and-places-clinical-trials-hold
[2] https://www.biopharmadive.com/news/sarepta-limb-girdle-gene-therapy-death/753419/