The FDA has accepted a supplemental new drug application seeking approval for selinexor for the treatment of patients with multiple myeloma following at least 1 previous line of therapy.
The FDA has accepted a supplemental new drug application (sNDA) seeking approval for selinexor (Xpovio) for the treatment of patients with multiple myeloma following at least 1 previous line of therapy, according to Karyopharm Therapeutics, Inc.1
The pharmaceutical company expects a decision from the FDA regarding the application before the end of the first quarter of 2021.
“This sNDA acceptance brings us one step closer to providing access to [selinexor] for a significantly larger patient population battling multiple myeloma,” Sharon Shacham, PhD, MBA, founder, president, and chief scientific officer of Karyopharm, stated in a recent press release. “If approved, we believe [selinexor] will become an important new, oral, once-weekly treatment option, used in combination with once-weekly [bortezomib (Velcade)], for patients with multiple myeloma after at least 1 prior line of therapy.”
Previously, in July 2019, selinexor was granted an accelerated approval for use in combination with dexamethasone in patients with relapsed/refractory disease who had received 4 or more prior therapies and whose disease is refractory to 2 or more proteasome inhibitors, at least 2 immunomodulatory agents, and a CD38-targeted monoclonal antibody.
The regulatory decision was based on data from a prespecified subgroup analysis of part 2 of the phase 2 STORM trial, in which the independent review committee–assessed overall response rate (ORR) reported with selinexor was 25.3% (95% CI, 16.4-36.0) based on the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma; notably, this was in 83 patients whose disease was refractory to bortezomib, carfilzomib (Kyprolis), lenalidomide (Revlimid), pomalidomide (Pomalyst), and daratumumab (Darzalex).2,3
The approval of the agent is contingent on the results from the confirmatory phase 3 BOSTON trial, which is evaluating the addition of the inhibitor of XPO1-mediated nuclear export to bortezomib and low-dose dexamethasone compared with bortezomib and low-dose dexamethasone alone in patients with relapsed/refractory multiple myeloma who were given 1 to 3 prior regimens.
Results from the trial were recently presented during the 2020 ASCO Virtual Scientific Program and showed that the selinexor triplet not only improved progression-free survival (PFS) and ORR in these patients, but it also reduced the incidence of peripheral neuropathy.4
Specifically, the triplet resulted in a median PFS of 13.93 months versus 9.46 months with the doublet (HR, 0.70; P = .0075). This benefit was observed across all subgroups, including patients whose tumors harbored 17p deletions and those who had previously received lenalidomide. The triplet also induced a significantly higher ORR compared with the doublet, at 76.4% versus 62.3%, respectively (P = .0012); this held true across all subgroups examined. Moreover, median overall survival had not yet been reached in the selinexor arm versus 25 months in the doublet arm (HR, 0.84; 95% CI, 0.57-12.3; P = .19).
Patients who received the triplet also experienced a response sooner than those who received the doublet, at 1.1 months versus 1.4 months, respectively. The median duration of response was also found to be longer with the selinexor triplet versus the doublet, at 20.3 months and 12.9 months, respectively. In the selinexor arm, the time to next treatment was a median of 16.1 months versus 10.8 months in the doublet arm (HR, 0.66; 95% CI, 0.50-0.86; P = .0012).
More patients in the control arm discontinued treatment because of disease progression compared with the investigational arm, at 52% versus 34%, respectively. A total of 47 patients on the selinexor arm died during the follow-up period compared with 62 patients on the doublet arm.
Additionally, investigators reported clinically important differences in motor, autonomic, and sensory scales in those who received selinexor. Rates of grade 2 or higher peripheral neuropathy were found to be significantly lower in the selinexor arm versus the doublet arm, at 21.0% versus 34.3%, respectively (P = .0013).
With regard to safety, the most frequently reported, grade 3 or higher, treatment-related adverse effects (AEs) with the triplet versus the doublet included thrombocytopenia, at 39.5% versus 17.2%, respectively; fatigue, at 13.3% versus 1.0%; and nausea, at 7.7% versus 0%. Seventeen percent of patients on the triplet arm discontinued treatment because of AEs versus 11% of those on the doublet arm.
More recently, in June 2020, the FDA approved selinexor for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, following at least 2 lines of systemic therapy.
“We look forward to working closely with the FDA during their review process and we sincerely thank the many patients, caregivers, and physicians whose immense contributions have helped us achieve this latest milestone,” added Shacham.
If marketing approval is obtained by the FDA for the third selinexor indication, Karyopharm plans to continue to commercialize the agent in the United States using its existing commercial infrastructure. The pharmaceutical company also plans to submit a marketing authorization application to the European Medicines Agency for the same indication later this year.