Sarepta Prices $300K Duchenne Drug As FDA Rift Emerges Over Approval

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asked her about her statements and was satisfied that “her decision is indeed based on her scientific evaluation of the evidence.”

Outside observers wanted more clarity.

“The one thing I would want to know was whether any member had a conflict of interest,” said Sheldon Krimsky, an adjunct professor of public health and medicine at Tufts School of Medicine. “This has happened in the past. It should be public information.”

Until a few months ago, the only data the FDA had on eteplirsen were from a tiny, 12-patient clinical trial. Those scant data compared patients on eteplirsen to a “historical control”—previous data on patients deemed to have similar characteristics to those who took the drug—but not to patients receiving a placebo in the study, which the FDA prefers. The agency’s clinical review team skewered Sarepta’s data, which they claimed didn’t provide the support needed to approve eteplirsen. Many sell-side analysts covering Sarepta gave eteplirsen little chance at approval. That’s why Sarepta’s shares shot up more than 70 percent when news of the thumbs-up broke on Monday.

Ellis Unger, director of the FDA’s office of drug evaluation-I, Luciana Borio, the FDA’s acting chief scientist, and John Jenkins, the director of the agency’s office for new drugs, all disagreed with Woodcock’s approval decision. Instead of the commissioner having final say, Lexchin argues that an independent person or entity should resolve cases that have “such a level of disagreement.”

The rift centered upon a protein, dystrophin, that Duchenne patients cannot produce. Woodcock and colleagues disagreed whether the dystrophin boost that eteplirsen produces is an adequate predictor of its eventual benefit to patients.

Part of the problem was flawed studies. Early data and anecdotes, publicized by Sarepta, turned out to be inaccurate. But they had already “fueled the public perception that eteplirsen is highly effective” as well as patients’ reluctance to participate in placebo-controlled trials, Unger wrote.

According to the FDA document, Woodcock recognized Sarepta’s studies were flawed, but she didn’t want to hold those flaws “against the patients.”

Woodcock’s staff questioned how much the pressure from politicians, patients, and advocates influenced her thinking. One of her staffers, left unnamed in the FDA document, said that her views “were not always clear during discussions throughout the review of the science—sometimes she seemed to agree with external constituents, sometimes not.”

Leaning more heavily on the needs and wishes of patients could soon gain greater traction at the FDA. Woodcock is a key proponent of more patient-centric drug evaluation. She is also a central figure in the political tussle to renew, by Congress every five years, the funding the FDA uses to pay for its drug reviews. (The money comes from fees paid by drug companies.) The current authorization ends in 2017. The renewal, called PDUFA in shorthand, is also a window to make changes, sometimes broad, sometimes minute, to the drug side of the FDA.

At a public meeting last month to discuss the upcoming renewal, Woodcock stumped for “tools that will enable patient groups, other stakeholders, the FDA, to collect meaningful patient input on what really matters to them as far as drug therapeutics so that we understand and regulators are applying a benefit-risk calculus that really reflects the position of the patients, what burden of disease means to patients, what relief they are seeking, what different adverse events mean to them, and so forth.”

Advocates for patients with other rare diseases have watched the Duchenne proceedings closely. Kenneth Hobby, the president of Cure SMA, which advocates for patients with spinal muscular atrophy, said that the eteplirsen ruling appears to signal a “new, more flexible and favorable viewpoint to the process for approval of therapies for rare diseases.”

“It will be interesting and important to see how the FDA will take this precedent and now apply it to other diseases,” he said. For the first time, an experimental therapy for SMA could be up for FDA approval next year.

In his eteplirsen decision, Califf was careful to write that no precedent is being set, and that each drug “must be evaluated on its own merits based on the totality of data and information.” But others at the FDA weren’t so sure.

Unger wrote that eteplirsen’s approval could have “profound” ramifications and “send the signal that political pressure and even intimidation—not science—guides FDA decisions, with extremely negative consequences.”

The FDA’s review team said it received many letters from the public and Congress, and some of them “used vulgar language and [were] abusive to the review staff.” At least two members of the agency’s review team left, or were leaving the agency because of those pressures and the scientific tug of war at the FDA. It’s unclear if the document was referring to Ronald Farkas, the head of the FDA’s eteplirsen review team. News surfaced last week that he had left recently. Farkas wasn’t named in the document released today, but CureDuchenne’s Miller said that when Farkas left, she “started feeling a lot more positive” about eteplirsen’s chances.

—Alex Lash contributed to this report

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