Independent committee favors continuing Elevidys dosing in trials
Sarepta said no changes to trial protocols recommended after patient death
An independent data monitoring committee (DMC) favors continuing dosing Elevidys (delandistrogene moxeparvovec-rokl) to people with Duchenne muscular dystrophy (DMD) in ongoing clinical trials, according to developer Sarepta Therapeutics.
The determination comes after recruitment and dosing in certain clinical trials were paused after a young man who received the gene therapy died due to acute liver failure. Sarepta said the new assessment was based on the therapy’s overall benefit-risk profile and that no changes to trial protocols have been recommended.
At the request of regulatory authorities in the European Union (EU), who requested the DMC meeting, Sarepta and Roche, which holds rights to Elevidys outside the U.S., will submit this information within a week. A decision on whether to lift the trials’s temorary halt will follow the EU regulatory process.
DMD is caused by mutations in the DMD gene that disrupt the production of dystrophin, a protein that helps protect muscle cells from damage during movement. The lack of functional dystrophin leads to progressive muscle weakness and wasting.
Elevidys is a one-time gene therapy designed to deliver a gene that codes for micro-dystrophin protein, which works like normal dystrophin, but is smaller in size. It uses a modified viral vector known as AAVrh74 that allows targeted delivery to muscle cells.
In ths U.S., the treatment is approved for people with DMD, ages 4 and older, who can walk, and has been granted accelerated approval for those in the same age range who can’t walk. Accelerated approval means there’s early evidence of benefit, but further clinical testing is required for full approval.
Risk of liver injury with Elevidys
Acute liver injury is a possible side effect of Elevidys and treatment may result in elevations of liver damage markers, typically in the first eight weeks. Elevidys’s prescribing label notes that patients with preexisting liver disease may be at higher risk of acute serious liver injury.
However, until the recent case, acute liver failure leading to death hadn’t been reported in more than 800 patients who received Elevidys as prescribed therapy or in clinical trials, Sarepta noted in its March update. Further testing showed the patient had had a recent infection with cytomegalovirus, which can damage the liver, that was deemed by a physician as a possible contributor to his death.
The clinical studies affected by the temporary halt include the Phase 3 ENVISION trial (NCT05881408) which is collecting safety and efficacy data on Elevidys in a wide group of DMD patients of different ages and walking abilities, and is still recruiting patients in Europe, Asia, and Australia.
Other studies are the Phase 2 ENVOL trial (NCT06128564) that’s testing Elevidys in DMD boys younger than 4 and enrolling at sites in Europe, and a Phase 1 trial (NCT06241950) of the antibody-cleaving therapy imlifidase as a pretreatment to Elevidys in DMD children with preexisting antibodies against the gene therapy’s viral carrier.
Meanwhile, patient monitoring and data collection continue for participants already enrolled. Sarepta doesn’t anticipate the pause to impact the studies’ timelines.
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