A supplemental New Drug Application has been submitted to the FDA for the use of selinexor as a treatment for patients with multiple myeloma following at least 1 line of prior therapy.
Karyopharm Therapeutics Inc. has submitted a supplemental New Drug Application (sNDA) to the FDA for the use of selinexor (Xpovio) as a treatment for patients with multiple myeloma following at least 1 line of prior therapy.1
The sNDA is based on findings from the phase III BOSTON trial, in which selinexor combined with bortezomib (Velcade) and low-dose dexamethasone led to a statistically significant increase in progression-free survival (PFS) compared with bortezomib/dexamethasone alone in patients with multiple myeloma who had received 1 to 3 prior lines of therapy. The median PFS was 13.93 months in the selinexor arm compared with 9.46 months with bortezomib/dexamethasone alone, translating to a 30% reduction in the risk of disease progression or death (HR, 0.70; P = .0066).
Selinexor is currently approved by the FDA for use in combination with dexamethasone for the treatment of adult patients with relapsed/refractory multiple myeloma who have received ≥4 prior therapies and whose disease is refractory to ≥2 proteasome inhibitors, ≥2 immunomodulatory agents, and a CD38-targeted monoclonal antibody.2
“Earlier this year, we reported positive top-line results from the pivotal Phase 3 BOSTON study evaluating the combination of Xpovio once-weekly Velcade and low-dose dexamethasone (SVd) as a second-line treatment for patients with relapsed or refractory multiple myeloma,” Sharon Shacham, PhD, MBA, founder, president and chief scientific officer of Karyopharm, stated in a press release.
“The full study results, which were included in the sNDA, will be presented on May 29, 2020, at the 2020 American Society of Clinical Oncology Virtual Scientific Program. In the BOSTON study, the SVd arm demonstrated a statistically significant reduction in the risk of disease progression or death, along with a 47% increase in median progression-free survival, as well as a significantly higher overall response rate, as compared to the standard Velcade and dexamethasone regimen. If approved, we believe Xpovio could become an important addition to the treatment paradigm for patients with relapsed or refractory multiple myeloma, and we look forward to working with the FDA during the review process,” added Shacham.
Selinexor is a first-in-class SINE (Selective Inhibitor of Nuclear Export) compound. The drug inhibits chromosomal maintenance protein exportin-1 (XPO1), a nuclear export protein that mediates the transport of more than 200 cargo proteins, including most tumor-suppressor proteins. The agent works to block the export process by binding to other proteins within the nucleus of the cell and shuttling them through the nuclear pores into the cytoplasm in the rest of the cell.
In the active comparator-controlled, open-label, multicenter phase III BOSTON study, investigators compared the efficacy, safety, and certain health-related quality of life (HR-QoL) parameters of once-weekly oral selinexor in combination with once-weekly bortezomib plus low-dose dexamethasone versus twice-weekly bortezomib plus low-dose dexamethasone in approximately 402 adult patients with relapsed/refractory multiple myeloma who have received 1 to 3 prior lines of therapy. Karyopharm previously reported that there were no new safety signals reported with selinexor in the BOSTON study compared with earlier research with the treatment.
The current approval of selinexor was based on data from a prespecified subgroup analysis of 83 patients of Part 2 of the multicenter, single-arm, open-label, phase II STORM trial. In this subpopulation, patients’ disease was refractory to bortezomib, carfilzomib (Kyprolis), lenalidomide (Revlimid), pomalidomide (Pomalyst), and daratumumab (Darzalex), and the benefit-risk ratio appeared to be greater in this more heavily pretreated subgroup than in the overall population with an ORR of 25.3%. Thirty-seven percent (n = 31) of patients had a minimal response or better to selinexor. This approval was an accelerated approval, meaning it is contingent on the results of a confirmatory trial.