Jenkins Delayed Retirement to Protect Drug Reviews from Woodcock
Former Office of New Drugs director John Jenkins delayed his planned retirement last year because he was worried that his boss, CDER director Janet Woodcock, would step in as acting director and damage the new drugs review program. This revelation comes from a new email released under a Freedom of Information Act lawsuit filed by New York University professor Charles Seife.
The email shows that the rift between CDER reviewers and Woodcock was much more serious than previously known. Written to then-FDA commissioner Robert Califf, the Jenkins email challenged Califf’s support of Woodcock’s decision to approve (see earlier story) Sarepta’s controversial Duchenne drug Exondys 51 (eteplirsen) last year. Jenkins complained in the email that Woodcock had written an approval memo before reviewers even submitted their review memo and summary. Previously, this and other disturbing actions were detailed in a review summary that illustrated her unprecedented involvement and interference in the eteplirsen review, actions that senior agency officials suggested were driven by her succumbing to Congressional, patient, company and other outside pressures to get the drug approved. Pressure from Woodcock and other outsiders was so bad that at least two members of the review team said they were leaving FDA or had done so, the summary indicated.
Jenkins told Califf that he was troubled by his agreeing to Woodcock’s analysis and by citing a “totality of evidence” standard for supporting eteplirsen’s approval. “That is not the statutory standard for demonstration of effectiveness and FDA has always stated that the statutory standard for demonstration of an effect on a surrogate endpoint for [accelerated approval] is the same as for regular approval (i.e., substantial evidence), Jenkins said. “Perhaps you are using ‘totality of evidence’ to support the decision that the data provided on the surrogate are reasonably likely to predict clinical benefit, but there must be substantial evidence of the drug’s effect on the surrogate and the data are very weak to meet that standard.
“You dismiss the concerns,” Jenkins continued, “about Janet’s level of involvement in this review and her role at the [advisory committee] by suggesting this is simply part of her leadership style. I have worked with Janet for over 20 years and I can say without a doubt that her involvement in this case far exceeds her usual ‘hands on’ approach. You note that there were 14 Center director briefings related to this case, that is clearly not the ‘norm’ for how CDER operates. You also suggest that because CDER has been successful under her leadership that suggests that her intense involvement in this case does not raise concern. I see that as true, true, and unrelated. The question in this case is not whether she has overall been an effective leader of CDER, but whether she acted appropriately and without bias in the current case, something I don’t think you effectively address given the evidence and the seriousness of the allegations and concerns expressed.”
Jenkins’s email also raised concerns about Woodcock’s “frequent private conversations with the sponsor and the stakeholder community. To my knowledge, she has not documented the substance of those conversations to the record, as is required under FDA regulations... The overall tone of your memo seems to say that you conclude that Janet behaved and conducted herself appropriately in this case. That is at odds with the experience of the review team and is counter to the team-based, collegial working environment that we hope to create at FDA so we can accomplish our important public health mission. This validation from your level of her actions and behavior is worrisome. 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.”
Asked by FDA Webview whether current FDA commissioner Scott Gottlieb has weighed in on the controversial nature of the drug’s approval, agency spokeswoman Sandy Walsh said he had not. “Dr. Gottlieb has not reviewed the approval decision personally, as the decision was made prior to his arrival at the agency,” she said. He has full confidence in Dr. Woodcock’s expertise and commitment to the FDA’s mission of public health promotion. Dr. Gottlieb fully supports Dr. Woodcock’s leadership of CDER and her leadership of the new drug program and the steps she is taking to modernize the agency’s approach to new drug regulation.”
Walsh confirmed that Woodcock is still serving as acting director of the Office of New Drugs while a search is on for Jenkins’ replacement. Jenkins retired in January after almost 25 years at the agency, and subsequently joined FDA regulatory consulting firm Greenleaf Health as principal for drugs and biologics (see earlier story).