FDA advisers recommend accelerated approval of a Sarepta gene therapy

Robert Weisman, The Boston Globe, May 12, 2023


A panel of advisers Friday recommended that the Food and Drug Administration speed up approving a Duchenne muscular dystrophy treatment developed by Cambridge biotech Sarepta Therapeutics, despite questions about its clinical benefit and safety.

By an 8 to 6 vote, the FDA advisers endorsed accelerated approval for the experimental gene therapy, called SRP-9001. The vote followed a daylong hearing, convened virtually, marked by sharp debate over the company’s clinical trial data and impassioned pleas from the parents of boys with Duchenne, a deadly muscle-wasting disease.

While acknowledging Sarepta’s clinical data raised questions, some advisers said they were swayed by videos shared by the parents of boys with Duchenne that showed improvement after being dosed with the gene therapy. Anthony Amato, a Harvard professor of neurology, said he saw “compelling evidence this was effective” for some patients.

But Caleb Alexander, a public health professor at Johns Hopkins, said the data “doesn’t rise to the threshold of substantial evidence.”

The vote is not binding on the FDA, which is set to rule later this month on Sarepta’s bid for faster approval. But the independent experts on the panel, called the Cellular, Tissue, and Gene Therapies Advisory Committee, are typically influential in the agency’s deliberations.

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Friday’s proceedings were being watched closely by patient advocates and other biotechs working on gene therapies for rare diseases. If the FDA grants Sarepta’s application, it would be the first accelerated approval for a gene therapy. That pathway allows earlier approval for drugs that treat a serious condition or fill unmet medical needs.

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In a public hearing before the advisory panel Friday, parents of boys in Sarepta’s clinical trial showed videos of their sons climbing stairs and playing baseball, testifying how they got better after infusion with the gene therapy. They warned any delay in approving Sarepta’s drug could cause further muscle loss in boys living with Duchenne.

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FDA staff reviewers, however, said the clinical trial data didn’t provide clear evidence of clinical benefit. They also raised concerns that the gene therapy might pose safety risks, such as liver injury, and that patients who get it might be ineligible for other clinical trials.

In the clinical data they reviewed, FDA staffers saw “no statistically significant difference between SRP-9001 compared to placebo” for all but the youngest patients, said Mike Singer, a clinical reviewer in the FDA’s Center for Biologics Evaluation and Research.

Singer also faulted Sarepta’s clinical data analysis. “The analysis wasn’t performed in a statistically rigorous way so we also can’t predict which patients would benefit” from the gene therapy, he said.

Another critic, health policy analyst Diana Zuckerman at the National Center for Health Research in Washington, warned that the FDA could lose credibility if it granted faster approval to a drug candidate before it had clear evidence it was safe and effective for patients.

“If the FDA no longer represents the gold standard for approval, that poses risks for all Americans with serious diseases,” she said.

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