Brief

FDA puts partial hold on Karyopharm's cancer drug

Dive Brief:

  • Karyopharm Therapeutics said March 10 it has responded to written notice from the Food and Drug Administration that clinical trials for the pharma’s oncology drug selinexor (KPT-330) have been placed on partial clinical hold.
  • Patients with stable disease or better may stay on selinexor therapy, the pharma said, but no new patients may be enrolled until the agency's partial clinical hold is lifted.
  • The FDA has indicated the hold stems from incomplete information in the original version of the investigator's brochure, including an incomplete list of serious adverse events associated with selinexor, Karyopharm said.

Dive Insight:

Karyopharma’s latest announcement of the FDA’s hold came only eight days after its stock fell 15% due to the March 2 news that its lead candidate, selinexor, failed to show statistical significance in a Phase 2 study of patients with relapsed/refractory acute myeloid leukemia.

At the FDA's request, Karyopharm said it has amended the investigator’s brochure, updated informed consent documents and, as of March 10, submitted all requested documents to the agency that should be required to lift the partial clinical hold. 

The Newton, Mass.-based pharma stressed that the hold isn’t due to any patient death or any new information on selinexor’s safety profile.  It noted that 1,900-plus patients thus far have been treated with selinexor in trials across a variety of hematological and solid tumor malignancies.

Jefferies analysts said in a note to investors that it all boils down to an administrative blunder.

"After speaking with management, we are comfortable this was purely an administrative error, does not at all reflect any new safety issue, and should not materially affect trial conduct/enrollment timelines," the analysts said in a March 10 research report. "We expect swift resolution and while perhaps not favorable for credibility, we see no impact to selinexor’s potential."

The FDA has 30 days to notify Karyopharm about whether the hold is lifted. The pharma said it is working diligently with regulators to get the hold removed and resume enrollment as expeditiously as possible. The company expects enrollment rates and timelines for its selinexor trials to remain materially unchanged.

Jefferies analysts said that in most of the trials, progressing patients are typically taken off the drug anyway, so this should not change the studies' integrity. Assuming things go smoothly, they said, the matter could be resolved in days to weeks and shouldn’t meaningfully change timelines.

Currently, selinexor, an oral selective XPO1 inhibitor, is being evaluated in several mid- and late-stage clinical trials across multiple cancer indications. Karyopharm said more Phase 1, 2 and 3 studies are ongoing or planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types.

Karyopharm sees a potential niche for selinexor in a competitive multiple-myeloma market.

In September, Karyopharm said mid-stage trial results showed a 20% tumor response rate in selinexor-treated multiple myeloma patients no longer responsive to several currently approved therapies. The company anticipates that selinexor’s efficacy in treating penta-refractory patients will help it win accelerated FDA approval.

In December, Karyopharm presented updated Phase 2b data on selinexor at the annual American Society of Hematology meeting. At that time, Jefferies analysts said that despite many available therapies, physicians at the meeting seemed to see potential added benefit from selinexor's clear single-agent activity and an oral pill should help with patient compliance.

Filed Under: Clinical Trials Regulatory / Compliance Corporate News