New FDA Elevidys label limits use to DMD patients who can walk
Update includes new safety warnings, precautions
The U.S. Food and Drug Administration (FDA) has approved an update to the prescribing information for Duchenne muscular dystrophy (DMD) gene therapy Elevidys (delandistrogene moxeparvovec-rokl), removing its conditional approval for DMD patients who can’t walk and including new safety warnings and precautions in light of two deaths related to the therapy reported earlier this year.
“We want to thank the FDA for their thorough and collaborative review,” Louise Rodino-Klapac, PhD, president of research and development and technical operations at Sarepta Therapeutics, the company that sells Elevidys, said in a company press release. The new label “will ensure that families and healthcare professionals have clear information, supported by a medication guide, to help understand these updates and guide treatment decisions.”
DMD is caused by mutations in the gene that encodes dystrophin, a protein that’s essential for muscle health. Elevidys is designed to deliver a gene encoding a shortened but functional version of this protein to muscle cells, with the goal of preserving muscle health and slowing disease progression. The treatment uses a modified virus to deliver the therapeutic gene.
The FDA first granted Elevidys accelerated approval (a type of conditional approval) in 2023 for certain children with DMD who can walk. The following year, the agency expanded its approval, granting full authorization of Elevidys for DMD patients ages 4 and older who can walk, as well as accelerated approval for nonambulatory patients in the same age range.
Elevidys’ approval was based in part on the Phase 3 EMBARK clinical trial (NCT05096221), which tested the gene therapy against a placebo in more than 120 boys with DMD. Although the study missed its main goal, which was to demonstrate improvements in a measure of motor function called the North Star Ambulatory Assessment, results showed Elevidys led to significant improvements in other measures of motor function, such as the time to walk a short distance or stand from a lying-down position. Long-term data from EMBARK have shown continued motor function gains two years after treatment.
Shipments halted
Sarepta announced earlier this year that two DMD patients, both nonambulatory, had died of acute liver failure after treatment with Elevidys. After the second death, the company suspended shipments of Elevidys for nonambulatory patients. An additional case of serious, but not fatal, acute liver injury has been reported.
The company also briefly halted shipments for ambulatory patients in July following the death of a patient in a clinical trial for a different Sarepta gene therapy, but shipments for ambulatory patients were resumed a few days later after safety reviews.
The updated prescribing information for Elevidys includes a boxed warning (the FDA’s most stringent safety warning) noting that the gene therapy can cause life-threatening liver injury. The update provides guidance aimed at minimizing the risk of this type of reaction, including instructions not to administer the therapy to anyone with signs of liver injury and requiring weekly monitoring of liver function for at least three months after Elevidys is administered.
The guidance also states that Elevidys shouldn’t be given to anyone who’s recently had an infection or received a vaccine. Infections and vaccines can activate the immune system, and liver injury related to Elevidys is thought to occur because the immune system reacts to the therapy’s viral vector, triggering inflammation that damages the liver.
Also included in the update is new guidance on the use of corticosteroids, anti-inflammatory medicines that are a staple of DMD treatment and are also used to help minimize inflammatory reactions against the therapy. The updated prescribing information includes details on how to use corticosteroids before and after Elevidys treatment, as well as a warning noting that the use of these and other immunosuppressing medicines may increase the risk of serious infections.
The FDA is also requiring Sarepta to conduct an additional observational study to assess the impact of Elevidys on liver health in approximately 200 DMD patients who will be followed for a year. Sarepta said it plans to launch a study testing a novel immune-suppressing regimen aimed at minimizing liver damage due to Elevidys, with the goal of seeing positive results that would allow resumption of Elevidys dosing for nonambulatory DMD patients.
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