FDA new drugs director slams Sarepta approval as ‘NOT a good model’

John Jenkins, who runs the FDA’s office for new meds, has not taken kindly to the regulator’s recent, and highly controversial, approval of Sarepta’s ($SRPT) Duchenne med Exondys 51 (eteplirsen) after hitting out at bad trials with questionable data.

In a presentation given this week at the NORD summit in Arlington, called “Lessons learned from eteplirsen and other recent rare disease programs,” Jenkins spoke specifically of the biotech’s drug, saying: the “path taken by Sarepta NOT a good model for other development programs.”

A month ago, the FDA approved Exondys 51 against all odds. The approval was considered unlikely because many of the data used to back a speedy approval were based largely on a small study of a dozen children with no placebo control, comparing eteplirsen’s results against historical data in the muscle-wasting disease.

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Back in April, an FDA panel of outside experts voted narrowly, 7 to 6, that Sarepta did not provide substantial evidence from “adequate and well-controlled” studies that the drug produced dystrophin at a level that was reasonably likely to produce a clinical benefit.

On the big question--do the clinical results of the single study provide “substantial evidence” of eteplirsen’s efficacy--seven of the panel members voted no, with three voting yes and three abstaining.

Five months down the line, however, it was approved, but as became apparent, this approval came at the cost of some major internal wrangling from within the agency.

In documents posted by the FDA along with its approval last month, the high level of lobbying undertaken by Dr. Janet Woodcock, the CDER director, for the med to be given the green light became clear.

It was, in the end, Dr. Woodcock who helped push the drug through to approval--despite internal protestations from Dr. Ellis Unger, a senior doc at the agency, among others, to FDA Commissioner Dr. Robert Califf.

Dr. Unger had expressed concerns at the small study size and its lack of clear efficacy, but Dr. Woodcock said the FDA must be “prepared to be flexible with respect to a devastating illness with no treatment options.”

Dr. Califf said he would “defer” to Dr. Woodcock in this case and allow the approval.

A few weeks before this decision, another strange thing happened when Dr. Ron Farkas, a fierce critic of Sarepta’s DMD drug, left the FDA unexpectedly to take on a consulting role at CRO Parexel ($PRXL), with no word from any party until reports of the move surfaced in the press, and each were forced to concede that he had moved on. Reasons for his departure were not given.

In his presentation, Jenkins set out his stall as to why the FDA on his watch isn't looking to lower standards--a concern many have voiced since the DMD approval. 

He reeled off the regulator's desired data list and what it wants, and doesn't want, to see: “In many cases, randomized controlled clinical trials represent the fastest way to determine if a drug is effective,” and that companies should “randomize as early as possible in development to avoid potentially misleading and uninterpretable findings from open-label trials.”

On the issue of being more flexible, as per Dr. Woodcock’s philosophy, he said: “Flexibility in FDA regulations does not mean marketing approval prior to demonstration of substantial evidence of effectiveness.”

He said that the FDA’s use of speedy reviews should be prospectively planned, “NOT as a ‘rescue’ for a failed program.”

He also said that personal attacks on FDA reviewers “creates an atmosphere of distrust and isolation rather than collaboration,” and that “recruitment and retention of qualified review staff is very challenging in such an environment.” In short, be nicer to the FDA, and see Sarepta as an exception to the rule.