Approval of Muscular Dystrophy Drug Causes Uproar at FDA

Agency official overrules staff’s protests

The FDA made history when it approved eteplirsen (Exondys 51, Sarepta Therapeutics), the first treatment for patients with Duchenne muscular dystrophy (DMD). But Janet Woodcock, director of the agency’s Center for Drug Evaluation and Research, overruled the protests of her staff to give eteplirsen the nod, and the FDA’s commissioner, Robert Califf, rubber-stamped her decision—resulting in near-mutiny at the agency, according to an article in Forbes.

One of the top officials in Woodcock’s division appealed the ruling, according to the article, and the agency’s chief scientist largely backed his conclusions, saying that “by any meaningful objective standard” the medication was unlikely to improve patients.

Ronald Farkas, the FDA staffer in charge of reviewing the new drug application for eteplirsen, has left the agency to take a job in industry.

After the controversial decision was announced, Eric Topol, chief academic officer at Scripps Research Institute in La Jolla, California, said the decision is “compromising reasonable approval standards.” Walid Gellad, an associate professor of medicine at the University of Pittsburgh who often serves on FDA panels, tweeted: “Let me summarize: a drug the FDA says has no clinical benefit will cost four times as much as a drug that cures hepatitis C.”

Eteplirsen was given the green light under accelerated approval, meaning that the FDA can withdraw its decision if future studies don’t confirm the drug’s benefit. Topol told Forbes that he wishes Congress had created a “conditional approval” designation, whereby eteplirsen could be immediately withdrawn from the market if it doesn’t work.

After an FDA advisory panel voted 7-to-6 to reject the drug, the agency and Sarepta agreed to take another look at dystrophin levels after 48 weeks of treatment. The results disappointed even Woodcock, according to Forbes. The data showed an increase of only 0.28% of normal levels, which was, on average, a tripling of dystrophin levels in the 12 boys that were studied. But the reviewers argued that, based on comparisons of different types of muscular dystrophy, an increase beyond 10% of normal would be needed to have a clinical impact on muscular dystrophy symptoms. Despite the disappointing data, Woodcock decided to grant accelerated approval right away, Forbes says.

Treatment with eteplirsen is expected to cost $300,000 per patient per year.

DMD is a rare muscular degenerative disease in boys that gradually and then rapidly leads to incapacitation, ultimately resulting in an early death.

Source: Forbes; September 20, 2016.