FDA Grants Selinexor Accelerated Approval Despite Concerns With Trial Data

The U.S. Food and Drug Administration (FDA) granted accelerated approval to for selinexor, an oral selective inhibitor of nuclear export (SINE), for patients with relapsed/refractory multiple myeloma (MM) who have received four or more prior therapies and whose disease has not responded to treatment with two or more proteasome inhibitors or immunomodulatory agents.

This approval comes after the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 8 to 5 against accelerated approval for selinexor in February. At the time, ODAC expressed concerns about the data from the single-arm, open-label, phase II STORM trial, and recommended delaying approval until the results of the phase III BOSTON trial became available. ODAC panelists believed that the BOSTON trial, which evaluated the safety and efficacy of bortezomib plus low-dose dexamethasone with or without selinexor, would address some of the issues with the STORM trial, and provide enough additional information for the FDA to make an informed decision regarding selinexor.

While the ODAC panel noted that selinexor did not demonstrate strong single-agent activity in the STORM trial, the reviewers expressed concerns about trial safety data.

The FDA’s approval decision was based on their review of safety and efficacy data from a prespecified subgroup analysis of STORM, which included 83 patients with heavily pretreated MM. The overall response rate was 25.3%, including one stringent complete response, four very good partial responses, and 16 partial responses. The median time to first response was four weeks (range = 1-10 weeks) and the median response duration was 3.8 months (range = 2.3 to not estimable).

The most common adverse events (AEs; occurring in ≥20% of patients) included thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection. Selinexor was approved with the FDA’s fast track and orphan drug designation, and, as a condition of accelerated approval, clinical trials are required to verify and describe selinexor’s benefit.

Source: FDA press release, July 3, 2019.