Karyopharm Therapeutics has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration seeking Accelerated Approval for XPOVIO (selinexor) in combination with ruxolitinib for patients with myelofibrosis.
The company has also requested Priority Review, which, if granted, could shorten the FDA review period to approximately six months.
If approved, selinexor plus ruxolitinib could become the first approved combination therapy for patients with myelofibrosis, according to Karyopharm.
Submission Supported by Phase 3 SENTRY Trial
The regulatory submission is supported in part by findings from the Phase 3 SENTRY trial (XPORT-MF-034; NCT04562389), which evaluated once-weekly selinexor plus ruxolitinib against placebo plus ruxolitinib in 353 patients with JAK inhibitor-naïve myelofibrosis.
At Week 24, 49.8% of patients receiving selinexor plus ruxolitinib achieved a spleen volume reduction of at least 35% (SVR35) compared with 28.0% of patients receiving ruxolitinib alone, meeting one of the trial’s co-primary endpoints.
The second co-primary endpoint, improvement in total symptom score, was not met, with symptom improvement observed in both treatment groups without a significant between-group difference.
An early overall survival signal was also reported. At approximately 12 months of median follow-up, the hazard ratio for death was 0.43 for selinexor plus ruxolitinib versus ruxolitinib alone, although longer follow-up is required to establish the durability and clinical significance of this finding.
Phase 3 SENTRY: Selinexor + Ruxolitinib Improved Spleen Responses in JAKi-Naïve Myelofibrosis
Accelerated Approval Pathway
Karyopharm is seeking Accelerated Approval based on the potential for SVR35 to serve as a surrogate endpoint reasonably likely to predict overall survival.
If accelerated approval is granted, the company plans to use long-term overall survival data from the ongoing SENTRY trial to confirm clinical benefit and support conversion to traditional FDA approval.
Karyopharm expects to receive the FDA’s decision regarding acceptance of the sNDA for review, as well as the anticipated regulatory timeline, in the fourth quarter of 2026, following the agency’s 60-day filing review period.
Selinexor previously received FDA Orphan Drug Designation for myelofibrosis in May 2022 and Fast Track Designation in July 2023.
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