FDA Advisory Panel Recommends Waiting for More Data Before Approving Karyopharm’s Selinexor

Shares of Karyopharm Therapeutics are crashing again after an advisory panel from the U.S. Food and Drug Administration (FDA) recommended delaying potential approval of the company’s experimental multiple myeloma treatment until additional data is available from an ongoing Phase III study.

The call to wait will set the company back a year for potential approval of selinexor, which had been granted priority review by the FDA. As could be expected, investors in the company were not happy and abandoned the stock. In premarket trading, shares of the company are down more than 17 percent to $4. The stock closed at $4.87 on Tuesday. The company is seeking approval of the treatment for a class of patients who do not have many benefits. The company is seeking approval of the drug for patients who have received at least three prior therapies.

On Tuesday, Karyopharm announced that the FDA advisory panel voted 8-5 recommending the FDA wait for the results of the Phase III BOSTON study evaluating selinexor in patients with relapsed or refractory multiple myeloma, before making a final decision regarding approval. That study has combined selinexor, a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, with Takeda’s Velcade (bortezomib) and low-dose dexamethasone. The late-stage study is comparing the combination against bortezomib and low-dose dexamethasone alone. Top-line data from the BOSTON trial are expected by the end of 2019 at the earliest, or into 2020, pending progression-free survival (PFS) events, a primary endpoint in this trial, the company said.

The advisory committee recommendation to delay potential approval of selinexor is not unexpected. Prior to the advisory committee meeting, an FDA briefing document for committee members indicated some significant concerns with the treatment. The release of that document also sent shares of Karypharm plunging earlier this week. The briefing document pointed to treatment with selinexor being associated with significant toxicity. As BioSpace reported, according to the FDA packet, 23 patients in the trial died within 30 days of study treatment. Of those, 13 died due to disease progression and 10 were due to a fatal treatment-emergent adverse event (TEAE). The FDA noted that all patients in the trial experienced at least one TEAE. The data shows that 93.5 percent of patients experienced at least one severe TEAE and 60.2 percent experienced at least one serious adverse event.

Karyopharm’s New Drug Application is based on data from the Phase IIb STORM trial that included 123 patients with RRMM who had received at least three prior treatments. Trial data showed an overall response rate of 25.4 percent, which included 23 patients who experience a partial response.

Sharon Shacham, president and chief scientific officer of Karyopharm, said the company is disappointed in the recommendation from the advisory panel. She said the company will work with the FDA to determine the best path forward for selinexor as the regulatory agency continues to review the company’s NDA. She said the company has submitted a “compelling, comprehensive clinical data package to the FDA supporting the request for accelerated approval for selinexor.”

The FDA is not bound by the recommendations of its advisory panels, but typically does follow the suggestions.

“Karyopharm remains committed to improving the outcomes of patients with cancer, including those with relapsed refractory multiple myeloma. Patients with triple class refractory multiple myeloma have disease which has progressed following treatment with the most effective myeloma drugs approved to date and are in desperate need of new treatment options.”