A Karyopharm Therapeutics multiple myeloma drug candidate faces longer odds for speedy FDA approval after the agency’s staff raised questions about the therapy’s efficacy and safety.
Staff concerns about Karyopharm drug selinexor were detailed in briefing documents posted Friday afternoon, ahead of an advisory committee meeting scheduled for Tuesday. Such panels are convened to assess the risks and benefits of new drugs, and to vote on whether to recommend approval.
Shares of Newton, MA-based Karyopharm (NASDAQ: KPTI) sank more than 43 percent on the news, closing at $5.07 on Friday.
Karyopharm developed selinexor to treat the most serious cases of multiple myeloma—patients whose disease has failed to respond to five earlier treatments. In a Phase 2 study enrolling such “penta-refractory” patients, Karyopharm reported that 25.4 percent of patients responded to treatment with selinexor and the corticosteroid dexamethasone. The company said the effect of the drug, a tablet, lasted a median 4.4 months.
However, FDA staff noted in the briefing documents that of the 23 patient deaths reported in the study, 10 of them (8.1 percent) were attributed to a fatal side effect from treatment. Staff added that all patients experienced at least one side effect from treatment, and 93.5 percent of patients experienced side effects that were severe.
FDA staff also raised questions about the clinical trial design, which tested the drug in a single group of patients without a control group for comparison. The staff noted that in the Phase 1 study, in which acute myeloid leukemia patients were randomized to receive selinexor or the physician’s choice of treatment, “there was worse overall survival in the selinexor arm, highlighting the toxicity of this drug.”
Karyopharm filed for accelerated approval, which means the FDA will review the drug with a thinner body of evidence to support it. When the agency approves drugs on that basis, it does so on the condition that a company conducts additional studies to confirm the earlier results. The advisory committee will vote on whether consideration of approval should be delayed until Karyopharm has results from a randomized Phase 3 study. That study is testing the Karyopharm drug in combination with another cancer drug, bortezomib, plus dexamethasone. That group of patients will be compared to a group treated with bortezomib and dexamethasone.
In a research note, RBC Capital Markets analyst Brian Abrahams wrote that the FDA staff’s concerns decrease the likelihood that the advisory panel will vote to recommend approval of selinexor next week. He added that there’s now more pressure on the Phase 3 study to produce better efficacy and safety data.
Results from the Phase 3 study of selinexor are expected in the fourth quarter of this year.