The US FDA has agreed that spleen volume reduction (SVR35) may support accelerated approval of selinexor (Xpovio) plus ruxolitinib in myelofibrosis, clearing the way for Karyopharm Therapeutics Inc. (Nasdaq: KPTI) to submit a supplemental New Drug Application (sNDA) in August. If approved, the combination would become the first approved combination therapy for myelofibrosis.
The planned submission follows written FDA feedback confirming that SVR35 is a reasonably likely surrogate endpoint (RLSE) for predicting overall survival, enabling the accelerated approval pathway. The decision is supported by data from the Phase III SENTRY trial (NCT04562389), which randomized 353 JAK inhibitor-naïve patients with myelofibrosis to receive selinexor plus ruxolitinib or placebo plus ruxolitinib.
The Phase III SENTRY trial met its primary endpoint, with 49.8% of patients receiving selinexor plus ruxolitinib achieving SVR35 at week 24 versus 28.0% with ruxolitinib alone (p<0.0001). The second co-primary endpoint, average change in absolute total symptom score (Abs-TSS) over 24 weeks, was not met. A secondary analysis showed an encouraging but immature overall survival trend. The results were presented as a late-breaking oral presentation at the 2026 American Society of Clinical Oncology Annual Meeting and simultaneously published in the Journal of Clinical Oncology.
The accelerated approval pathway allows Karyopharm to seek approval based on SVR35 while continuing blinded follow-up from SENTRY to confirm an overall survival benefit. The study does not permit patient crossover, strengthening the ongoing survival analysis. Karyopharm also intends to request Priority Review, which, if granted, could result in an FDA decision approximately six months after the application is accepted for review.