While FDA commissioner Rob Califf was trying to navigate an internal civil war at the agency over its controversial decision to provide an accelerated approval for Sarepta’s eteplirsen, John Jenkins, then head of the Office of New Drugs, sent him a memo which detailed a blistering attack on CDER chief Janet Woodcock.
It was Woodcock who demanded, and won, the argument in favor of an accelerated OK of the Duchenne muscular dystrophy drug.
But Jenkins, who sided with other top officials at the FDA in opposing the approval, says that Woodcock created an “appearance of bias” in pushing for the approval from an early point. Woodcock, he wrote Califf in a memo dated September 14, 2016, left the FDA review team feeling pressured to come over to her side. And she bypassed the usual chain of command to get what she wanted, insisting on an approval even before the review team had completed its task and leaving them distrustful of her role and manner.
Not only did Jenkins object to Woodcock’s handling of eteplirsen, a drug which had the vocal support of the Duchenne community, he also told Califf that he had delayed his retirement specifically because Woodcock intended to take his place after he left. And that is exactly what she did.
While Califf published much of the documentation around the dispute, this particular memo did not surface until Seife’s FOIA lawsuit forced it out. And it includes the remarkable suggestion that Califf should counsel the powerful CDER chief on her manner and her methods.
Jenkins has since retired from the FDA, but he declined to talk to Seife, as did Woodcock. But his memo deserves careful attention. One excerpt:
On page 4, you state “there is also abundant evidence that Dr. Woodcock heard and read FDACDER0001 all the scientific evidence…” This implies she took these actions BEFORE reaching a decision on the application, which is clearly not correct given her statement to the review team of her intention to overrule them and approve the drug BEFORE they had completed their reviews. Keep in mind this occurred after an AC (advisory committee) meeting at which the majority of the panel voted against both AA and full approval. It is also clear that she was prepared to approve the drug over the team’s objections by the original PDUFA goal date and only reluctantly agreed to press the sponsor for additional data on dystrophin production from the ongoing open-label trial. While I am glad she agreed to go along with that request, convincing her to take what seemed like a very logical action was not easy. So, I find it hard to reconcile your statements about the process with the actions taken. Keep in mind that the usual course of action would be for the Office to issue a CR letter and then the sponsor could submit a FDRR that would first come to me and only if I supported the Office would an FDRR go to the Center Director. In this case that process was bypassed.
His memo goes on to outline his concerns about the complete lack of data on efficacy as well as concerns that accelerated approval would clearly lower the bar at the agency on a new drug OK.
Also on page 9 it is ironic that you attribute to Janet the idea of randomizing early in order to generate good evidence. That is exactly what the review team planned to require of Sarepta after the results of the 12-patient study became available, but it was Janet that pressed that a new randomized trial not be required. So, if Janet had followed the normal CDER process in this case the review team would have required placebo-controlled trials, as they did for drisapersen and we would have better data on which to make a decision.
Jenkins stops one step short of accusing Woodcock of bullying the staff.
While I understand your desire not to undercut her role as Center Director, her actions have at best created a serous …appearance of bias among the review team members and that has created distrust and a sense of undue pressure to “come around” to her way of thinking. Even if you uphold her decision I would think you should counsel her about how her behavior and actions have undermined her credibility among the review staff and should be avoided in future similar cases. Effective leaders must have the trust and respect of their staff.
Later, just before he retired, Jenkins gave a speech in which he tried to warn other drug developers to avoid trying to follow the same path that Sarepta took. But he was clearly concerned about the future:
As you know, I had planned to retire from FDA last spring. I have delayed my departure for a variety of reasons, but one of the most important reasons is that Janet has told me she plans to serve as acting in my place as head of OND once I leave. I am very concerned about the impact of that decision on the future of the new drugs review program and would be happy to discuss those concerns further.
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