Karyopharm Therapeutics recently announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending conditional approval for xpovio (selinexor), in combination with dexamethasone, for the treatment of adult patients with relapsed/recurrent 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, and whose disease progressed on their last line of therapy. The CHMP's opinion will now be submitted to the European Commission (EC) for review, which is expected to make a final decision within two months.
Xpovio is the first and only approved nuclear export inhibitor (SINE), and it is also the first approved drug targeting a novel target for myeloma (XPO1) since 2015. Furthermore, Xpovio is the first oral monotherapy for the treatment of DLBCL.
Selinexor, the world's first oral selective nuclear export inhibitor (SINE), has been approved in the United States under the brand name Xpovio for the treatment of two major indications in hematological malignancies: multiple myeloma (MM) and diffuse large B-cell lymphoma (DLBCL). Recently, the National Medical Products Administration (NMPA) of China has also accepted the New Drug Application (NDA) for selinexor in the treatment of patients with refractory relapsed multiple myeloma (rrMM).
In the European Union, the Marketing Authorization Application (MAA) for selinexor is 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.
The results showed that the study met its primary endpoint: an overall response rate (ORR) of 26% (95% CI: 19-35) with oral selinexor treatment. 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. The median OS was 15.6 months in patients who achieved clinical benefit (≥minimum response), compared to only 1.7 months in patients with disease progression or unevaluable response (p < 0.0001).
Karyopharm's application for conditional approval in Europe was based on the same criteria used for 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. Because the benefit-to-risk ratio appeared higher in this more severely affected, multi-response population than in the overall trial population, the overall response rate (ORR) was 25.3%. In July 2019, the U.S. FDA approved Xpovio in combination with low-dose dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma (rrMM). In June 2020, the FDA further approved Xpovio as a monotherapy for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). In December 2020, the FDA approved a supplemental New Drug Application (sNDA) for Xpovio, expanding its indication to include the treatment of patients with multiple myeloma (MM) who have received at least one prior line of therapy.
