In an 8-to-5 vote, the U.S. Food and Drug Administration’s (FDA’s) Oncologic Drug Advisory Committee (ODAC) decided against recommending accelerated approval of selinexor for treatment of patients with relapsed/refractory multiple myeloma (MM), citing the difficulty of determining whether the benefits outweigh the risks.
Karyopharm Therapeutics, the manufacturer of the first-in-class, oral selective inhibitor of nuclear export (SINE) compound, reported data from the phase IIb STORM (Selinexor Treatment of Refractory Myeloma) Part 2 study, which evaluated the drug in combination with low-dose dexamethasone in patients with penta-refractory MM.
STORM Part 2 enrolled 122 patients and met its primary objective, with an overall response rate of 26.2 percent, and a median response duration of 4.4 months. However, 95.1 percent of participants experienced at least one grade 3/4 adverse event, the most common of which were thrombocytopenia, anemia, neutropenia, hyponatremia, and fatigue. Nearly 30 percent of patients discontinued treatment due to toxicity.
ODAC recommended that the FDA await results from the randomized, open-label phase III BOSTON study, which is evaluating bortezomib and dexamethasone with or without selinexor in relapsed and refractory MM, before deciding on approval. Results of the BOSTON study are expected in the first half of 2020.
“I believe there is a probable benefit of selinexor-dexamethasone for some [patients with] triple class-refractory myeloma, and of course I completely understand the urgent need to develop novel agents with novel mechanisms of action for these patients,” committee member Alice T. Shaw, MD, PhD, director of thoracic oncology at Harvard Medical School told MedPage Today. “But … there are real toxicities with this combination.”
While not bound by the decisions of the advisory committee, the FDA often follows its recommendations.