US FDA Approves Selinexor (Xpovio) For Treatment of Relapsed Or Refractory Multiple Myeloma.
The US FDA has approved a new drug, Selinexor to treat patients with relapsed or refractory multiple myeloma, overruling a panel of external cancer experts who expressed concerns about its toxicity. The FDA approval was under an accelerated, or conditional, approval based on a single-arm clinical trial showing a 25% tumor response rate. The patients enrolled in the clinical trial had advanced multiple myeloma no longer responsive to at least four prior therapies.
The new multiple myeloma drug, called Selinexor, will be marketed by Karyopharm Therapeutics under the brand name Xpovio
and is actually combined with the corticosteroid dexamethasone.
The approval of selinexor, a nuclear export inhibitor, applies to adult patients with multiple myeloma who have received at least four prior therapies and whose disease is resistant to at least two proteasome inhibitors, two immunomodulatory drugs and an anti-CD38 monoclonal antibody.
There is no cure for multiple myeloma only FDA-approved treatments to target the cancer and slow down the spread of the disease. Often over time, patients exhaust all available treatments and still see their disease progress. The approval of selinexor provides a treatment option for patients with multiple myeloma with no available therapy.
The fast approval was based on results from the phase 2b STORM study, which analyzed selinexor in combination with dexamethasone among a subgroup of 83 patients with relapsed refractory multiple myeloma. Results showed an overall response rate of 25.3% among patients in the subgroup. Median time to first response was 4 weeks (range, 1-10) and the median duration of response was 3.8 months.
The same 2b STORM clinical trial also raised concerns about Xpovio’s safety, including reductions in platelets and white blood cell counts that caused serious, potentially fatal bleeding and infections.
A panel of external oncologists convened by the FDA recommended against Xpovio’s approval, concluding the drug’s benefits did not outweigh its safety risks. The vote was 8-5 against the drug. Some specialists on the panel, however, believed the drug should be approved given the need for new drugs to treat multiple myeloma patients who have run out of other treatment options.
The Xpovio label approved by the FDA mentions the drug’s toxicity and advises oncologists to reduce dosing when certain side effects are noted. The label also states that Xpovio’s “continued approval” is dependent on “verification and description of clinical benefit in a confirmatory trial.” Karyopharm is conducting a randomized, controlled Phase 3 study of Xpovio in multiple myeloma patients, with a readout expected by the end of 2019. The primary goal of this trial is to determine if Xpovio can delay tumor progression and improve overall survival compared to current treatment protocols.
Common adverse effects associated with Selinexor and dexamethasone include leukopenia, neutropenia, thrombocytopenia, anemia, vomiting, nausea, fatigue, diarrhea, fever, decreased appetite, constipation, upper respiratory infections and hyponatremia.