Karyopharm Therapeutics recently announced that the European Commission (EC) has conditionally approved Nexpovio (selinexor), in combination with dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy and whose disease is refractory to at least two proteasome inhibitors (PIs), two immunosuppressants (IMiDs), and one anti-CD38 monoclonal antibody, or whose disease progressed on their last line of therapy.
This approval is based on data from the Phase IIb STORM trial. Based on data from the Phase 3 BOSTON trial, the company plans to submit a second regulatory application in the EU in April 2021 to expand the indication for Nexpovio to patients with multiple myeloma (MM) who have received at least one line of prior therapy.
In the EU, the Marketing Authorization Application (MAA) for selinexor was based on data from the Phase IIb STORM study. This was an international, multicenter, single-arm, open-label study that enrolled 122 patients with three classes of drug-refractory multiple myeloma who had previously received multiple therapies, with a median of seven prior regimens, including a median of ten unique antimyeloma drugs.
Results showed that the study met its primary endpoint: an overall response rate (ORR) of 26% (95% CI: 19–35) with oral selinexor. According to IMWG criteria, 16 patients (13%) achieved a minimal response (MR), and 48 patients (39%) had stable disease (SD). All responses were adjudicated by an independent review committee. The median overall survival was 8.6 months (95% CI: 6.2–11.3) across the entire population. Among patients who achieved clinical benefit (≥ minimal response), the median OS was 15.6 months, while in patients with disease progression or unevaluable response, the median OS was only 1.7 months (p < 0.0001).
Karyopharm's conditional approval in Europe was based on the same criteria as Xpovio's accelerated approval by the FDA in the United States. Specifically, it included efficacy and safety data from a pre-specified subgroup analysis of 83 patients in the STORM study whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab. The benefit-to-risk ratio appeared higher in this more severely affected, multi-response population than in the overall trial population, with an overall response rate (ORR) of 25.3%.
Regarding Xpovio Approval:
In July 2019, the FDA approved Xpovio in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM). In June 2020, the FDA reapproved Xpovio as oral monotherapy for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). In December 2020, the U.S. FDA approved a supplemental New Drug Application (sNDA) for Xpovio, expanding its indication for the treatment of patients with multiple myeloma (MM) who have received at least one prior line of therapy.
Notably, Xpovio is the first and only approved nuclear export inhibitor (SINE), and the first approved drug targeting a novel myeloma target (XPO1) since 2015. Furthermore, Xpovio is the first oral monotherapy for the treatment of DLBCL.
Recently, the National Medical Products Administration (NMPA) of China has accepted a New Drug Application (NDA) for selinexor for the treatment of patients with refractory relapsed multiple myeloma (rrMM). This is the first NDA submitted in mainland China for a SINE series compound, marking a significant step closer to this new treatment option for Chinese hematological malignancy patients.
