Newton, Mass. — Karyopharm Therapeutics Inc. has submitted a supplemental New Drug Application 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 six months.
“Today’s submission is an important step toward our goal of bringing the combination of selinexor plus ruxolitinib to patients with myelofibrosis who continue to face a significant unmet need,” said Reshma Rangwala, M.D., Ph.D., Chief Medical Officer and Head of Research at Karyopharm. “The SENTRY trial generated compelling and consistent results, including rapid, deep and sustained spleen responses across a broad range of patients, together with a promising overall survival signal and important evidence of disease modification. We believe the strength of these data underscores the potential of this novel combination to deliver meaningful long-term benefits and fundamentally change the treatment of patients with myelofibrosis.”
The application is based in part on data from the Phase 3 SENTRY trial, which evaluated selinexor plus ruxolitinib against placebo plus ruxolitinib in patients with myelofibrosis who had not previously received a JAK inhibitor.
Karyopharm said the data support a positive benefit-risk profile for the combination and include a promising overall survival signal.
For accelerated approval, the FDA would need to determine that a spleen volume reduction of at least 35% is reasonably likely to predict an overall survival benefit. Karyopharm plans to use longer-term survival data from SENTRY to confirm clinical benefit and potentially support conversion to traditional approval.
The company expects to receive the FDA’s decision on whether to accept the application for review, along with anticipated review timelines, in the fourth quarter of 2026 following the agency’s 60-day filing review period.
The Phase 3 SENTRY trial enrolled 353 patients with myelofibrosis and platelet counts above 100 x 10⁹/L. Participants were randomized 2-to-1 to receive once-weekly selinexor plus ruxolitinib or placebo plus ruxolitinib.
The trial’s co-primary endpoints were a spleen volume reduction of at least 35% at week 24 and the average change in total symptom score over 24 weeks compared with baseline.
Results from SENTRY were presented at the 2026 American Society of Clinical Oncology Annual Meeting and published in the Journal of Clinical Oncology. The findings were also presented at the 2026 European Hematology Association Congress.
Selinexor received FDA Orphan Drug Designation for myelofibrosis in May 2022 and Fast Track Designation in July 2023. The European Commission granted Orphan Medicinal Product Designation for the treatment in October 2022.
Myelofibrosis is a rare blood cancer that causes scarring of the bone marrow, interfering with the production of healthy blood cells. The disease can also cause an enlarged spleen, anemia, fatigue, night sweats and bone pain.
XPOVIO is an oral inhibitor of the nuclear export protein XPO1 and is already approved in the United States for several multiple myeloma treatment settings.
