Death of Elevidys Patient Rattles Duchenne Community

The death of a teenager with Duchenne muscular dystrophy (DMD) following treatment with the gene therapy Elevidys (delandistrogene moxeparvovec-rokl) is sparking concerns and uncertainty within the rare disease’s patient community.

Sarepta Therapeutics announced the patient’s death on March 18. The company said the patient had suffered acute liver failure and noted that acute liver injury is a known potential side effect of Elevidys and other adeno-associated virus (AAV)-mediated gene therapies.

“Although it is not a new safety signal and the benefit-risk of Elevidys remains positive, acute liver failure leading to death represents a severity of acute liver injury not previously reported for Elevidys, which to date has been used to treat more than 800 patients in clinical trials or as a prescribed therapy,” the company said, in a press release.

The Boston Globe reported that the patient was a 16-year-old boy. The company did not respond to a request for comment from Managed Healthcare Executive.

Elevidys is currently the only FDA-approved gene therapy for patients with Duchenne muscular dystrophy. It was first approved in June 2023. At the time, Peter Marks, M.D., Ph.D., the head of the FDA’s Center for Biologics Evaluation and Research, noted that there was “an urgent, unmet medical need” in Duchenne muscular dystrophy. The agency said it was aware of the risks associated with the drug, but argued that they were counterbalanced by the life-threatening and debilitating nature of the disease.

The original approval, which came via the FDA’s Accelerated Approval pathway, pertained to patients 4 through 5 years of age with a confirmed mutation in the DMD gene. Last year, that approval was expanded to all patients at least 4 years of age, including both ambulatory and non-ambulatory patients. The healthcare news site STAT reported that Marks had signed off on the expanded approval over the objections of review teams and some staffers who questioned the therapy’s benefits.

In its announcement of the patient death, Sarepta said that testing showed the patient had a recent cytomegalovirus infection and noted that the virus can cause liver damage. They said the patient’s treating physician had identified the infection as a possible contributing factor to the patient’s death.

Still, the news has sparked consternation among stakeholders, including patient groups and industry players.

The patient advocacy group Parent Project Muscular Dystrophy (PPMD) said there is an “urgent need to understand the risks associated with gene therapy in our current therapeutic landscape to ensure patient safety.” However, the group also reaffirmed their commitment to working together with industry partners and regulatory agencies to push for strong safety protocols and advances in DMD care.

Pat Furlong

Pat Furlong, the group’s president and CEO, said the patient’s death was “a tragedy beyond words.”

“We recognize the courage it takes for families to pursue new treatment options in the fight against Duchenne,” she said, in a press release. “At PPMD, and as a community, we remain committed to advocating for transparency, safety, and ongoing research to ensure that every individual has the information they need to make informed decisions.”

Meanwhile, the company’s share price on the Nasdaq stock exchange dropped by nearly 30% after the news broke. A week later, the price had yet to recover.

Elevidys is one of four DMD therapies from Sarepta currently approved by the FDA. According to the company’s website, it currently has four other DMD therapies in its pipeline, including two RNA-targeted therapies and two gene-editing therapies. The company is also working to develop gene therapies for limb-girdle muscular dystrophy.