Ryoncil approval in September seemed like almost a sure thing, but it wasn't. But it is also true that you can't rule out the possibility of accelerated approval or EUA for one or more indications based on our recent trial results.

Look how incredibly "inflexible" they were about this approval:

https://www.ashclinicalnews.org/online-exclusives/fda-grants-selinexor-accelerated-approval-despite-concerns-trial-data/

FDA grants accelerated approval
to selinexor for multiple myeloma

Thursday, July 11, 2019

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.


https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-selinexor-multiple-myeloma

FDA grants accelerated approval
to selinexor for multiple myeloma

On July 3, 2019, the Food and Drug Administration granted accelerated approval to selinexor (XPOVIO, Karyopharm Therapeutics) in combination with dexamethasone for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

Efficacy was evaluated in 122 patients enrolled in Part 2 of STORM (KCP-330-012; NCT02336815), a multicenter, single-arm, open-label study of patients with RRMM who had previously received three or more anti-myeloma treatment regimens including an alkylating agent, glucocorticoids, bortezomib, carfilzomib, lenalidomide, pomalidomide, and an anti-CD38 monoclonal antibody. In addition, the disease was refractory to glucocorticoids, a proteasome inhibitor, an immunomodulatory agent, an anti-CD38 monoclonal antibody, and to the last line of therapy. These patients were treated with selinexor (80 mg) in combination with dexamethasone (20 mg) on days 1 and 3 of every week.

The approval was based on efficacy and safety in a prespecified subgroup analysis of 83 patients whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab. The overall response rate was 25.3% (95% CI: 16.4, 36), with 1 stringent complete responses (CR), no CR, 4 very good partial responses and 16 partial responses. The median time to first response was 4 weeks (range: 1 to 10 weeks). The median response duration was 3.8 months (95% CI: 2.3, not estimable). The efficacy evaluation was supported by additional information from an ongoing, randomized trial in patients with multiple myeloma.

Common adverse reactions reported in at least 20% of patients include thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

The recommended selinexor dose is 80 mg in combination with dexamethasone taken orally on days 1 and 3 of each week.

View full prescribing information for XPOVIO.

As a condition of accelerated approval, further clinical trials may be required to verify and describe selinexor’s benefit. FDA granted this application fast track designation and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.