Sarepta Therapeutics Inc.’s stock plunged 44 percent Thursday after Food and Drug Administration staff again expressed reservations about its proposed drug for Duchenne muscular dystrophy.
The experimental therapy would be the first medicine to treat a mutation causing the fatal muscle-weakening genetic disorder, rather than just alleviate symptoms. The disease affects roughly one in every 3,500 boys.
But in a briefing document released in advance of a key gathering Monday of an FDA advisory committee, agency staffers wrote that the clinical data submitted by Sarepta “overall did not provide statistical evidence to support the efficacy” of the drug, called eteplirsen.
Sarepta’s shares closed down $8.69 at $11.02 on Nasdaq.
Staffers who reviewed the evidence for eteplirsen will present their findings to the advisory committee, a panel of independent medical authorities meeting in Hyattsville, Md., that is expected to make a recommendation to the FDA early Monday evening. The agency, which will decide next month whether to approve the treatment, considers its safety and effectiveness. It usually, but not always, follows the recommendation of its advisory committees.
Sarepta, whose own medical experts also will address the advisory panel Monday, contended in its own briefing document that the benefits of the therapy outweigh its risks to patients.
“This clinical benefit is accompanied by a safety profile that indicates that eteplirsen is well tolerated with no apparent signal of safety risks,” the Sarepta document said.
It acknowledged that the number of patients studied was relatively small, so the study may have missed some risks, but said “this needs to be weighed against the certainty of relentless disease progression and premature death for boys with [Duchenne] without treatment.”
FDA staffers criticized Sarepta’s clinical study design and statistical analysis Thursday, echoing many of the points they made in an earlier document prepared before a scheduled meeting of the advisory committee in January, which was postponed because of a blizzard.
Among other things, they argued that the Cambridge drug maker overestimated how much of a protein, known as dystrophin, was produced by eteplirsen and how much the drug helped the boys who took it on a six-minute walk test. Representatives from Sarepta did not respond to an e-mail requesting a response to the FDA staff briefing document.
CureDuchenne, a California nonprofit group dedicated to finding cures for muscular dystrophy, released a statement expressing disappointment. The group, which provided early-stage funding for eteplirsen, supports approval of the drug.
“While we understand the FDA needs to make sure drugs are safe and effective, we also know the consequence of inaction for those with Duchenne,” the group said in its statement. “We are hopeful for accelerated approval.”
Sarepta has submitted fresh information to the FDA since the staff briefing document appeared in January, challenging the earlier staff analysis. But in their new document, staffers made it clear that “we do not agree with the applicant’s characterization of inaccuracies in the initial FDA briefing document.”
Joseph P. Schwartz, an analyst for the Boston health care investment bank Leerink Partners, urged caution in a note to investors Thursday morning.
“Consistent with our cautious stance, the updated FDA briefing documents ahead of the eteplirsen [hearing] remain largely negative citing concerns with trial design, efficacy, dystrophin measurement methods, and laboratory measurements and statistical analysis,” he wrote.
More than 800 patients and members of their families are expected to be at Monday’s meeting, making it one of the best-attended FDA hearings on a proposed drug in history.
Highlighting the intense scrutiny on next week’s advisory committee meeting, Janet Woodcock, director of the FDA’s center for drug evaluation and research, is scheduled to appear before the panel.Robert Weisman can be reached at firstname.lastname@example.org. Follow him on Twitter @GlobeRobW.