Sarepta resists as FDA seeks pause on Elevidys use

Sarepta has refused to suspend all dosing of its gene therapy for Duchenne muscular dystrophy, Elevidys, defying a clinical hold request from the FDA.

The FDA said it had met with Sarepta to ask that it voluntarily stop all shipments of Elevidys (delandistrogene moxeparvovec), following reports of a third death involving one of the company's adeno-associated virus (AAV) gene therapies – two involving the DMD therapy and a third involving a patient treated with an experimental candidate for limb-girdle muscular dystrophy (LGMD) – from acute liver failure.

"The company refused to do so," said the US regulator in a statement, with both FDA Commissioner Marty Makary and Center for Biologics Evaluation and Research (CBER) Director Vinay Prasad pledging to "take steps" to protect patients from potentially unsafe therapies.

For its part, Sarepta confirmed it would continue to ship Elevidys to ambulatory DMD patients, having already suspended its use in frailer, non-ambulatory patients – the group in which both Elevidys-related fatalities occurred.

The company said it had seen no "new or changed safety signals" in the ambulatory DMD population that would warrant a complete halt to dosing, adding: "We look forward to continued discussions and sharing of information with FDA in order to advance our shared purpose of protecting patient safety and informed access to care."

It pointed out that Elevidys remains the only approved gene therapy for DMD, a rare, progressive, and ultimately fatal disease.

"Most importantly, the choice to be treated with Elevidys should remain with patients, families, and their doctors," said the company.

The case will be keenly watched as a vanishingly rare example of a company defying a request by the regulator for a voluntary suspension. The next move by the FDA could be to order a mandatory product recall, which it has the power to do, but that would be challengeable in the courts, with the onus on the agency to prove it has solid grounds for the action.

The FDA has also removed 'platform technology designation' for Sarepta's AAV gene therapy programme, a status introduced last year that can provide a streamlined pathway through development and regulatory review.

For Sarepta, the request comes at a challenging time for the company. It has just slashed a third of its workforce – around 500 jobs – and retreated from gene therapy development in order to focus on small interfering RNA (siRNA) drug candidates.

Roche-partnered Elevidys is a key source of income, with sales of around $282 million in the second quarter out of total product revenues of $513 million. News of the FDA action pushed its already-depressed share price 36% to just over $14, a fraction of its highs of around $150 last year.

"Families and advocates who once championed Elevidys now grapple with a mix of disappointment and concern for those treated patients affected with severe liver failure," said patient advocacy group Cure Duchenne in a statement.

"As regulatory agencies intensify their scrutiny, the path forward for Elevidys remains fraught with questions about safety, accountability, and a re-evaluation of its risk-benefit calculation," it continued.

"Researchers and policymakers are now weighing whether current frameworks for reporting adverse events and monitoring long-term safety are robust enough. Families deserve access to all the available data in order to make appropriate decisions about Elevidys, as well as any treatment option or clinical trial opportunity."

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