Karyopharm filed an sNDA for selinexor plus ruxolitinib in myelofibrosis, seeking FDA accelerated approval and Priority Review.
Written By: Rishabh Sonawane, BPharm
Reviewed By: Pharmacally Editorial Team
Karyopharm Therapeutics has submitted a supplemental New Drug Application (sNDA) to the U.S. FDA for XPOVIO (selinexor) plus ruxolitinib in patients with myelofibrosis, seeking accelerated approval based in part on Phase 3 SENTRY data. The company has also requested Priority Review, which, if granted, could shorten the FDA review period to six months following formal filing acceptance.
Regulatory Submission Builds on Phase 3 SENTRY Data
The submission follows pre-sNDA discussions with the FDA after topline results from SENTRY (XPORT-MF-034; NCT04562389), a Phase 3 trial evaluating once-weekly selinexor 60 mg in combination with ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis.
Karyopharm believes the SENTRY findings support a positive benefit-risk profile for the combination, including a promising overall survival signal and evidence of potential disease modification.
Under the accelerated approval pathway, the FDA would need to determine whether spleen volume reduction of at least 35% (SVR35) represents a surrogate endpoint reasonably likely to predict clinical benefit, including overall survival. The company plans to use ongoing long-term survival data from SENTRY as confirmatory evidence to verify clinical benefit and support conversion to traditional approval.
Selinexor Targets XPO1-Mediated Nuclear Export
Selinexor is an oral, first-in-class inhibitor of exportin 1 (XPO1), a major nuclear export protein that mediates the transport of numerous proteins and RNAs from the nucleus to the cytoplasm, including tumor suppressor proteins. By selectively inhibiting XPO1, selinexor alters the nuclear localization and activity of proteins involved in cellular growth and survival.
Myelofibrosis is a rare blood cancer characterized by progressive bone marrow fibrosis, impaired blood-cell production, splenomegaly and systemic symptoms including fatigue, abdominal discomfort, early satiety, night sweats and bone pain.
JAK inhibitors, including ruxolitinib, remain the only approved class of therapies for myelofibrosis, leaving a significant unmet need for additional treatment approaches and combination strategies.
SENTRY Evaluated Spleen and Symptom Outcomes
SENTRY enrolled 353 JAK inhibitor-naïve patients with myelofibrosis and baseline platelet counts above 100 × 10⁹/L. Patients were randomized 2:1 to receive either selinexor 60 mg once weekly plus ruxolitinib or placebo plus ruxolitinib.
The trial’s co-primary endpoints were SVR35 at Week 24 and the average change from baseline in absolute total symptom score (Abs-TSS) over 24 weeks.
Karyopharm reported rapid, deep and sustained spleen responses across a broad patient population, alongside a promising overall survival signal. The company is using these findings to support its regulatory case for accelerated approval.
SENTRY data were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the Journal of Clinical Oncology. Additional results were presented at the 2026 European Hematology Association (EHA) Congress, where the presentation was recognized among the meeting’s six best abstracts.
FDA Decision Timeline
Karyopharm expects the FDA to determine whether the sNDA is accepted for filing during the fourth quarter of 2026, following the agency’s standard 60-day filing review period. If accepted and granted Priority Review, the application could receive an FDA action within six months.
Selinexor has received FDA Fast Track and Orphan Drug Designations for myelofibrosis, while the European Commission has granted Orphan Medicinal Product Designation for the indication.
If accelerated approval is granted, Karyopharm plans to use longer-term overall survival follow-up from SENTRY to verify clinical benefit and support conversion of the indication to traditional approval. The company expects to continue discussions with the FDA during the review to finalize the confirmatory evidence plan.
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About the Writer
Rishabha Sonawane, B.Pharm (LinkedIn) is healthcare writer with a strong interest in medical writing, regulatory affairs, clinical research, and AI-driven drug discovery. He has completed specialized training from the NIH and ICMR in clinical pharmacology, clinical research, and scientific writing. Passionate about evidence-based healthcare communication, he focuses on translating complex scientific research into clear, accurate, and engaging medical content.