Why Did FDA Approve Controversial Muscular Dystrophy Drug Exondys 51?

Newly released documents shed light on agency’s thinking

The release of internal FDA documents related to its approval of the Duchenne muscular dystrophy (DMD) drug Exondys 51 (eteplirsen), developed by Sarepta Therapeutics, suggests that Dr. Janet Woodcock, director of the agency’s Center for Drug Evaluation and Research (CDER), took into account Sarepta’s financial problems when making her controversial decision, according to a report from BioSpace.

Exondys 51 was given the green light in September, but there was significant turmoil within the FDA over the action. The agency’s acting chief scientist, Dr. Luciana Borio, and Dr. Ellis Unger, director of the office of drug evaluation, strongly opposed the approval, arguing that Sarepta did not provide sufficient evidence to support the efficacy of Exondys 51 in DMD. Dr. Ronald Farkas, clinical team leader, exited the agency just prior to the approval.

But Woodcock pushed it through, overruling her staff, BioSpace reports. The final decision then went to Dr. Robert Califf, the FDA’s Commissioner, who sided with Woodcock.

The recent release of internal memos indicates that on September 14, Unger sent a note to Califf saying that he had analyzed the sparse evidence for the drug’s dystrophin production, and that Woodcock did not take this information into consideration. “I think it will be important for the regulatory record to reflect that there was no scientific basis underlying the conclusion of ‘reasonably likely’ [to be effective] in this case. This was simply a judgment call by Dr. Woodcock.”

Boria also sent documentation criticizing Califf for ignoring the “minuscule” amount of data that Sarepta had provided to support the approval.

Before the release of the FDA documents, there had been suggestions that part of Woodcock’s considerations involved Sarepta’s financial position—essentially arguing that if the drug didn’t get approved, the company’s stock would crash, and Sarepta wouldn’t be able to continue working on promising DMD research. The newly released information seems to support that line of thinking, according to BioSpace.

Sources: BioSpace; November 4, 2016; and CDER Documents; November 2016.