FDA asks Sarepta to stop shipping Duchenne gene therapy

The Food and Drug Administration has asked Sarepta Therapeutics to halt all shipments of its marketed gene therapy for Duchenne muscular dystrophy over safety concerns, the agency confirmed Friday.

Sarepta has rejected the agency’s request, however, and will continue to ship doses of its therapy, Elevidys, to some younger patients — a decision that puts the company in direct confrontation with its regulator.

Sarepta last month paused shipments for certain older Duchenne patients following the death from acute liver failure of a second teenager treated with Elevidys. The FDA subsequently began a formal investigation of Elevidys’ liver risks.

Reuters first reported news of the FDA’s request Friday afternoon, which BioPharma Dive initially confirmed with a source familiar with the matter. Both Sarepta and the FDA issued statements later on Friday evening.

“We believe in access to drugs for unmet medical needs but are not afraid to take immediate action when a serious safety signal emerges,” said FDA Commissioner Martin Makary in the agency’s statement.

Earlier in the day, Makary told Bloomberg in an interview Friday that his agency is weighing whether to withdraw Elevidys from the market entirely. The FDA on Friday also halted several Sarepta clinical trials.

“Based on our comprehensive scientific interpretation of the data, which shows no new or changed safety signals in the ambulant patient population, we will continue to ship Elevidys to the ambulant population,” Sarepta said in its statement. Duchenne patients who can still walk are usually younger.

The news comes on the heels of Sarepta reporting this week the death of a 51-year-old man who received an experimental gene therapy it’s developing for another kind of muscular dystrophy known as limb-girdle. The man died of complications from acute liver failure in June.

Sarepta said it informed the FDA of this death on July 3, a timeline that means the agency has known of it for more than two weeks.

While Elevidys and the experimental therapy are constructed differently, they both use the same kind of engineered virus to deliver a replacement gene to the body’s muscles.

The FDA appears to now be focusing on this virus, known as AAVrh74, revoking a so-called “platform therapy designation” that was meant to speed development and evaluation of new treatments using AAVrh74 as a delivery tool.

Elevidys was approved by the FDA in 2023 as the first gene therapy for Duchenne, a genetic disorder that results in progressive muscle weakening and typically early death. Its clearance was a milestone, coming after decades of painstaking research, but also controversial, as the evidence Sarepta compiled in support didn’t prove a clear benefit on patients’ motor function.

The FDA expanded Elevidys’ approval the next year, allowing a substantially larger group of patients to receive it, including those whose disease had eroded their ability to walk. Both decisions were contentious, sparking internal disagreements between FDA reviewers and Peter Marks, then the head of the FDA office that reviews gene therapies.

While sales initially grew quickly, they’ve slowed this year as safety concerns mounted after the first patient death in March and the second in June.

Liver toxicity is a known risk of gene therapies like Elevidys and the other, called SRP-9004, that Sarepta is developing for limb-girdle. Treating muscular dystrophies can require large doses, which is thought to raise the chances of dangerous liver side effects.

After the second death, Sarepta began working on a new regimen of immune-suppressing drugs it hopes will make treatment safer. And on Wednesday, the company announced the FDA would require a new black box warning on Elevidys’ liver risks.

During a conference call Wednesday, Sarepta executives claimed the warning would resolve any agency concerns with the treatment’s use in younger Duchenne patients who can still walk. But the FDA’s action Friday contradicts Sarepta’s confidence and threatens to upend the company’s business.

Sarepta held the Wednesday call to discuss its plans to lay off approximately 500 employees and stop research on a number of experimental limb-girdle gene therapies, which company CEO Doug Ingram said was necessary to ensure the company’s “long-term viability.”

Neither Ingram nor other executives who spoke on the call disclosed the most recent patient death, despite having learned of it weeks ago and more recently informed regulators, trial investigators and patient groups. BioCentury was the first to report the death on Thursday evening, and Sarepta later confirmed it during a Friday morning call, during which analysts expressed frustration for having been kept in the dark.

Ingram claimed the death was “neither material nor relevant” to the information it shared on Wednesday and defended the company’s track record of being “extraordinarily transparent.”

A few hours after the call’s conclusion, Reuters reported the FDA’s plans to request Sarepta stop treating patients with Elevidys.

Editor’s note: This story was updated Friday with additional detail and context, and again on Saturday with details of Sarepta’s response.

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