After Controversial Drug Decision, FDA Tries Transparency

Posted November 4, 2016 at 4:47pm

The decision to approve a controversial rare-disease treatment has haunted the Food and Drug Administration in recent weeks. But instead of shying away from the controversy, the FDA has been remarkably transparent about how the decision was made. On Thursday night, the agency laid bare the disagreements between its highest officials by releasing 300 pages of internal emails and on Friday, FDA Commissioner Robert Califf addressed the debate.

In September, the FDA approved a drug for Duchenne muscular dystrophy, an inheritable disease that is fatal in young boys. The agency was under pressure to approve the drug from Congress and the patient community, even though there was limited evidence suggesting that the drug worked. In the days after the decision, FDA reviewers went public with their concerns and a picture emerged of an agency in turmoil.

Speaking at a conference on Friday, numerous FDA officials addressed the decision. The FDA’s release the night before of e-mails offered a glimpse into the debate between top officials in the days leading up to the approval announcement. The FDA’s candor about the controversy seems to be an effort to put it in the rearview mirror and reassure the public that the approval of drugs with uncertain benefits will not become commonplace.

“We’ve moved on,” John Jenkins, head of the FDA’s office of new drugs, told reporters Friday. “The good news is, most decisions we make within the agency are not this controversial. There is generally lots of agreement and lots of consensus around the decisions we’re making.”

Jenkins spoke at a daylong conference hosted by the Friends of Cancer Research and Prevision Policy, a firm that tracks health and regulatory issues.

Califf, the FDA commissioner, similarly played down the controversy Friday. “I hope people realize that a great thing for a federal agency that has to make hard decisions is to encourage people that have differences of opinion to express them,” he said.

Jenkins and other FDA officials opposed the approval of the drug, eteplirsen, which is supposed to treat Duchenne muscular dystrophy. Much of the evidence in the drug’s application was based on a clinical trial of only 12 people – a sample size that is without precedent in FDA history. While the drug was found safe, the FDA’s reviewers were skeptical that the drug actually worked to delay the disease’s progression.

Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, felt that the evidence did show that the drug was effective, and overruled the recommendation by the reviewers. Califf said that as a political appointee, he did not feel that it was appropriate for him to alter Woodcock’s decision.

In one of the documents released Thursday, Ellis Unger, the acting director of the FDA’s office of drug evaluation, expressed concern that Woodcock had made her decision before reviewing all relevant scientific evidence. Unger feared that the decision would set a precedent “where accelerated approval could be provided for a rare disease based solely only on the medical and scientific judgment/opinion of the Center Director, as was clearly the case here,” he wrote in an e-mail to Califf.

Jenkins sided with Unger on the eteplirsen decision and has publicly pushed back against the idea that other drugs will be approved in a similar fashion.

However, that concern could play out in other decisions for rare disease drugs with active patient lobbies. At the conference Friday, the question of evidence standards was posed to Richard Pazdur, an FDA official who is setting up a new center devoted specifically for the development of cancer treatments. For cancer drugs, the FDA already uses more flexible standards and approves applications based on small sample sizes, and Pazdur acknowledged that sometimes the agency has to be “creative” with the approvals.