Karyopharm Therapeutics Inc. announced the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the conditional approval for NEXPOVIO® (selinexor) in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy. The positive CHMP opinion is a scientific recommendation for marketing authorization and one of the final steps before the European Commission (EC) makes a decision on Karyopharm's marketing authorization application (MAA). An EC marketing authorization through the centralized procedure is valid in all 27 European Union member countries as well as the European Economic Area countries Iceland, Liechtenstein and Norway. The MAA is supported by data from the Phase 2b STORM study which evaluated selinexor in patients with heavily pretreated, triple class refractory multiple myeloma and published in the New England Journal of Medicine (Chari, et al.) in August 2019. Karyopharm intends to submit a second regulatory filing to the EMA (Type II variation) by April 2021 based on the data from the confirmatory Phase 3 BOSTON study, which evaluated once-weekly NEXPOVIO in combination with once-weekly Velcade® and low-dose dexamethasone in patients with multiple myeloma after at least one prior therapy with the goal of further expanding the global reach of NEXPOVIO to additional patients in need of new treatment options. The Phase 2b STORM trial (Selinexor Treatment of Refractory Myeloma) was an international, multi-center, single-arm, open-label study which enrolled 122 patients (Part 2 of the trial) with heavily pretreated, triple class refractory multiple myeloma. Patients in the trial had a median of seven previous therapeutic regimens, including a median of 10 unique antimyeloma agents. For the study's primary endpoint, oral selinexor achieved an overall response rate of 26% (95% confidence interval [CI], 19, 35) and the trial therefore met its primary endpoint. Minimal response per IMWG criteria was observed in 16 (13%) patients and 48 patients (39%) had stable disease. All responses were adjudicated by an Independent Review Committee. The median overall survival was 8.6 months in the total population studied and 15.6 months in patients who had a minimal response or better. Karyopharm's request for conditional approval in Europe is based upon the same patient population that served as the basis for XPOVIO's accelerated FDA approval in the U.S. Specifically, it includes the efficacy and safety data from a pre-specified sub-group analysis of 83 patients in the STORM study whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab, as the benefit-risk ratio appeared to be greater in this more heavily pre-treated population than in the overall trial population. The overall response rate in this patient population was 25.3%. The most common adverse reactions (=20%) were thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.