Duchenne muscular dystrophy eats away at muscle tissue.
Photograph by Huntstock—via Getty Images/DisabilityImages
By Sy Mukherjee
April 26, 2016

Shares of Cambridge, Massachusetts-based biotech Sarepta Therapeutics (srpt) plummeted by as much as 46% in early Tuesday trading after an independent panel of FDA advisers issued a series of negative votes on Monday against eteplirsen, the firm’s experimental drug for Duchenne muscular dystrophy (DMD), a rare degenerative condition. The advisory committee’s critical opinions could derail the therapy’s chances of winning FDA approval.

DMD is an X chromosome-linked genetic disorder that almost exclusively affects boys and eventually leaves the vast majority of patients wheelchair-bound as it slowly ravages their muscles and motor functions. While survival rates have improved somewhat over the years, many patients still die by their mid-20s.

The dearth of Duchenne treatment options has catalyzed a groundswell of patient activism in recent years, especially as two firms—Sarepta and fellow orphan drugmaker BioMarin (bmrn)—chased competing treatments for the condition. But the DMD community was dealt a blow at the beginning of the year when the FDA rejected BioMarin’s therapy.

All eyes then turned to Sarepta, and patient groups lined up an aggressive pro-eteplirsen PR campaign aimed at persuading the FDA and its advisers to green light the therapy.

Monday’s public advisory committee meeting was among the most heavily-attended such events in recent memory. It featured a staggering 52 speakers (nearly all of whom urged the expert panel to recommend eteplirsen’s approval). Many who spoke were patients or family members of patients, and their testimony was often deeply personal.

“FDA, please don’t let me die early!” said one young patient in one particularly blunt moment.

But after a 12-hour marathon of pleas from patients and Sarepta representatives, the FDA panel ultimately voted 6-7 against an endorsement of eteplirsen’s ability to create dystrophin (the protein that Duchenne patients have trouble creating) on a level that would clinically benefit patients.

Panel members also questioned the design of several of the clinical studies that Sarepta used to argue for eteplirsen’s approval. While the FDA isn’t obligated to follow advisory committees’ recommendations, it usually does (as the agency did with BioMarin’s therapy).

Monday’s turn of events underscores the inherent clashes between Americans who must grapple with devastating diseases on a daily basis and the regulators who are expected to leave emotion at the door and hew to the available empirical evidence when weighing approvals.

Still, in recent years, the FDA has been on a drug approval binge, including 45 new drugs in 2015 alone. Some of those approvals have courted controversy, such as the female libido medication Addyi, which showed modest effects and safety concerns in trials but still won the FDA’s blessing on the heels of a concerted political campaign to push more sexual enhancement drugs for women.

Eteplirsen’s supporters argued on Monday that even a slight demonstrated clinical benefit should justify marketing approval given the lack of alternatives and the serious practical difficulties of developing therapies for rare diseases. Critics retorted that Sarepta’s data and trial design was at fault.

“We would like to thank the hundreds of patients and families who participated in the discussion today, underscoring the critical unmet need of people living with Duchenne,” said Sarepta interim CEO Edward Kaye in a statement.

“We appreciated the opportunity to present our data to the advisory committee panel and will continue to work with FDA as they complete their review of the eteplirsen NDA. Today more than ever, we remain committed to our mission of bringing a treatment to the Duchenne community.”


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