Ipsen wins FDA AdComm rare disease vote in split decision despite doubts about its data

An FDA advisory committee voted 10 to four in favor of Ipsen’s rare disease drug palovarotene, despite members of the panel expressing significant concerns with the data. The vote boosts the prospects of the French drugmaker finally starting to deliver a return on its $1 billion bet on the drug candidate.

After discussing the data for hours, the FDA asked the panel of experts whether phase 3 results show the drug candidate is an effective treatment in patients with the rare bone disease fibrodysplasia ossificans progressiva. Ten panel members said yes, resulting in Ipsen winning the vote, but some also raised significant concerns about the data presented.

Thomas Weber, M.D., a professor at Duke University Medical Center, voted yes but said “the post-hoc analysis obviously is inherently flawed, and there are confounders that we can't adjust for.” Despite such problems, Weber concluded that the totality of the data support “adequate effectiveness.”

Elizabeth Chrischilles, Ph.D., a professor at the University of Iowa, gave a positive appraisal, noting the “consistency of findings across many appropriate sensitivity analyses” and “the quality of the external control group.” Suzanne Robotti, founder of the medicine side effect-focused nonprofit MedShadow Foundation and the panel's acting consumer representative, summed up the overall tone of the meeting: “The drug is effective. I don't know how effective.”

Robotti said that on previous committees she has voted no “because the data just wasn't clear enough.” This time, Robotti overlooked her doubts about the data. “I don't have the stomach for that with this drug. With this population, there's a small window because the damage accumulates and small differences can make big differences, so I voted yes.”

Michael Blaha, M.D., director of clinical research at Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, was among the experts to vote no. Blaha looked for evidence of symptomatic benefit but only found an imaging endpoint that suggested palovarotene has a positive effect. 

“While part of the disease process, I just wasn't 100% convinced that that imaging endpoint of a certain amount of calcification … was enough for me to say that there was an unequivocal benefit for these patients,” Blaha said. The physician added that it would be “a tragedy” if palovarotene isn’t studied further but decided that, as it stands, the evidence didn’t support a yes vote.

The FDA now has until mid-August to decide whether to approve palovarotene. While the vote went in Ipsen’s favor, the mixed comments on both the yes and no sides suggest the final verdict may still be in the balance. Before the vote, Lisa Yanoff, M.D., a deputy director at the FDA, told the panelists to “keep in mind that your comments are often more important to us than your vote.”