Advisers urge FDA to delay decision on Karyopharm cancer drug
Advisers to the US drugs regulator have said a decision on whether to approve Karyopharm’s multiple myeloma combination should be delayed until the results of a phase 3 trial, due late this year or in 2020.
The FDA’s Oncologic Drugs Advisory Committee (ODAC) was discussing Massachusetts-based Karyopharm’s combination involving selinexor, a first-in-class, oral selective inhibitor of nuclear export (SINE) compound.
Karyopharm is asking for approval in combination with dexamethasone for patients with relapsed refractory multiple myeloma who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody.
In other words, most of the other approved options out there, such as Takeda’s Velcade (bortezomib), Celgene’s Revlimid (lenalidomide), and Janssen’s Darzalex (daratumumab) respectively.
The FDA had granted a priority review lasting only six months, and the manufacturer is seeking approval based on early data, that would need to be confirmed by larger trials.
This filing is based on data from Karyopharm’s phase 2b STORM study, testing selinexor and low-dose dexamethasone in 122 heavily pretreated patients refractory to three classes of drugs, and who had been exposed to all five of the most commonly prescribed medicines to treat the disease.
The study met its primary goal of overall response rate (26.2%), including six very good partial responses and 24 partial responses.
But the ODAC voted 8 to 5 recommending the FDA should wait for results from Karyopharm’s randomised, open-label, phase 3 BOSTON study before making a final decision on approval.
Enrolment is complete on the study and top-line data are expected by the end of this year at the earliest, or into 2020, depending on how long patients stay alive without the disease spreading.
While votes from the FDA’s advisers are not binding, the regulator usually follows their advice. The regulator is due to make a decision on selinexor before 6 April this year.
Shares in Karyopharm ticked down on the Nasdaq stock exchange following the committee’s decision – trading had been halted while the committee deliberated.
However, most of the damage had already been done as shares had dived following comments from FDA reviewers in a briefing document posted before the meeting.
Reviewers had raised concerns about reliability of efficacy data from single-arm trials such as STORM, toxicity, and whether patients can tolerate the proposed starting dose.
Karyopharm has also asked for conditional approval from European regulators.
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