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.
Selinexor is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound manufactured by Karyopharm Therapeutics. ODAC’s decision is based on a review of 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. The overall response rate (the study’s primary objective) was 26.2 percent, and patients experienced 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.
The FDA is not required to follow the advisory committee’s recommendations, but the agency often adheres to its decisions. On March 14, the FDA extended the review period of selinexor’s new drug application, setting a new action date of July 6.