An influential advisory committee narrowly declined to recommend US sale of an experimental treatment for Duchenne muscular dystrophy Monday, disappointing hundreds of patient advocates who argued for approval of the medicine.
The panel of medical experts concluded in a 7-6 vote that a clinical study by Cambridge biotech Sarepta Therapeutics Inc. failed to meet the Food and Drug Administration’s standard for accelerated approval. In a separate 7-3 vote, with three members abstaining, the committee determined that Sarepta’s clinical trial was poorly designed and didn’t prove the drug candidate was effective in treating the fatal muscle-wasting disease.
Coming at the end of a 12-hour meeting marked by emotionally-charged testimony from boys with Duchenne and family members, the nonbinding votes leave the fate of Sarepta’s drug, called Eteplirsen, in the hands of the FDA. The agency, which is set to rule on the drug application by May 26, historically has relied heavily on its advisory committees for guidance.
Summing up a widely held view on the panel, committee member Aaron S. Kesselheim, associate professor at Harvard Medical School in Boston, said “the studies provided by [Sarepta] were not adequate and well controlled.” But he acknowledged that it remains an “open question” whether Eteplirsen produces a clinical benefit to patients who take it.
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Parents of boys with Duchenne were sobbing after the meeting, but some said they refused to abandon hope for the drug’s approval.
“It’s not over,” said Debra Miller, founder of the advocacy group CureDuchenne. “It wasn’t just the panel that heard the patient testimony. The FDA heard it, too, and their mandate is to listen to the patient perspective.”
A number of boys who took the drug in Sarepta’s study testified at an overflowing hearing Monday that it was effective in slowing progression of the disease. They called on the advisory panel, meeting in Hyattsville, Md., to recommend it be allowed on the US market.
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“It lets me feed myself,” said 17-year-old Austin Leclaire of Pembroke, one of dozens of Duchenne patients, family members, and doctors from around the country who spoke in favor of approval. “It keeps my brother] Max walking. It gives us a chance. . . . It’s time to listen to the real experts. So to make that easier, we brought them here today. Please use them.”
“The worst thing you can do is deny access to a drug and then find out that it works after we’ve lost a generation of boys,” said Miller, whose 19-year-old son Hawken is a student at the University of Southern California.
Earlier in the day, scientists from Sarepta clashed with FDA regulators over their conflicting interpretations of findings from Sarepta’s clinical trial — with FDA staffers questioning whether there was clear evidence that the company’s drug was slowing progression of the disease and contending they had warned Sarepta the design of its trial was flawed.
While applauding the packed audience for being “passionate and invested,” William Dunn, director of the division of neurology products at the FDA’s Center for Drug Evaluation and Research, said the agency has a responsibility to approve drugs based on scientific proof of their safety and effectiveness. “Anecdote and emotions don’t change the data,” he said.
Monday’s meeting was the most closely watched FDA hearing in years on a proposed therapy, with advocates arguing failure to approve the drug could not only worsen life for Duchenne patients but also discourage biotechs from developing drugs to treat other rare diseases.
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“There is a very human cost to making a determination that a drug doesn’t work when it really does,” said patient advocate Christine McSherry, whose 20-year-old son Jett suffers from Duchenne. She said boys who took part in the trial experienced fewer spontaneous falls — a common symptom of the disease — and less fatigue than others.
The drug produces a protein known as dystrophin that is missing in boys with Duchenne. It would be the first medicine to treat the genetic cause of the disease rather than just symptoms. The disease strikes one in 3,500 boys, who typically lose the ability to walk by age 12 and don’t live past age 25. Sarepta’s drug would treat about 13 percent of those boys who have a specific gene mutation.
But the FDA scientists questioned whether Sarepta’s small clinical study, which enrolled only 12 patients, adequately demonstrated an increase in dystrophin.
They also criticized the company for relying on historical “control data,” comparing the progress of boys in their study to those of a similar age who had the disease in the past, rather than giving some boys in the study a placebo. Sarepta maintained there weren’t enough patients qualifying for the study to conduct a so-called placebo-controlled study where patients wouldn’t know if they were given the drug or not.
FDA officials “consistently and strongly encouraged” a placebo-controlled trial and “expressed strong doubts regarding the interpretability of comparison” to historic data, FDA clinical team leader Ronald Farkas told the advisory committee.
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Sarepta chief executive Edward Kaye said the study showed Eteplirsen was effective with little safety risks to the boys taking it.
“The data clearly demonstrate that Eteplirsen is working as intended. . . .” Kaye said. “The observed increase in dystrophin results in a clinically meaningful benefit.”
Trading in Sarepta shares was halted by the Nasdaq stock exchange Monday while the advisory committee considered the company’s drug candidate.
Underscoring the high stakes of the meeting, Janet Woodcock, the FDA’s director of drug evaluation, attended in person. Without taking a position on the Sarepta data, she noted that the company’s experimental drug was granted an accelerated approval process for unmet medical need treatments in which “more uncertainty is going to be tolerated” than in conventional drug approvals.
Robert Weisman can be reached at robert.weisman@globe.com. Follow him on Twitter @GlobeRobW.