The Karyopharm team $KPTI took on a tough challenge on Tuesday, trying to overcome an overwhelmingly critical review by FDA regulators in winning over a panel of outside experts brought in to review their pitch for an accelerated approval of selinexor for multiple myeloma.
They lost, but nevertheless found considerable support for this drug among the panelists.
The panel voted 8 to 5 against an approval, saying affirmatively that the FDA should take a wait-and-see attitude until the randomized pivotal study wraps toward the end of the year.
Karyopharm’s stock — battered last Friday — took another tumble after the bell, dropping 19%.
FDA representatives were polite about it, but outlined multiple problems with the data that Karyopharm presented: Missing data due to dropouts, unacceptable real world evidence, an absence of evidence of positive single agent activity (there are negative results), mostly partial responses and much, much more — all information that the biotech failed to spotlight in the lead-up to the NDA. In one study the FDA cited, the overall survival rate was worse in the selinexor arm.
Then there was the toxicity profile, with a high frequency of treatment emergent adverse events among patients taking the drug. The agency cited a 94% rate of grade 3 or grade 4 adverse event. 10 deaths were due to a fatal adverse event in the main single arm study used for the accelerated approval. And 9 in 10 patients required a dose modification, with a majority requiring 2 modifications.
Given the limited efficacy and toxicity, the FDA asserted, “it is unclear whether the benefit outweighs the risk.”
That’s not something you want to hear in a panel review.
Meanwhile, a pivotal trial is underway, and if a patient demanded it, there are avenues that patients could use to get the drug without an accelerated approval.
The FDA’s oncology panel is not a tough group, on average, to win over. There’s a big appetite for new drugs to treat cancer patients who have failed multiple therapies, and a low bar on safety. Not getting past that at this stage will likely set the bar higher for when Karyopharm comes back with their pivotal data — provided that the agency goes ahead and rejects it, as they have clearly indicated that they plan to.
The significant number of votes in Karyopharm’s favor, despite the FDA’s position, does underscore just how anxious many of these experts are about offering early approvals, even when multiple drugs are approved for the same indication. The bias is in favor of more options, which was clearly on display here.
Dana Farber’s David Harrington joined the minority in favor of providing an accelerated approval. “The data are not conclusive in either direction,” he said, but…”I think we do patients some potential benefit if this is used constructively.”
Just a slight nudge in its favor from regulators may well have been enough to win an approval, despite the trial issues. And that once again gets back to whether the developers have a close working relationship with the agency.
The biotech’s case wasn’t good enough, though, with the majority siding with the regulators who have the final say now. Toxicity was a major issue with the experts who sided against a quick OK.
At best, Karyopharm likely faces a lengthy delay refiling an NDA. And that is if the Phase III data are positive.
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