FDA Receives sNDA for Selinexor Plus Ruxolitinib in Myelofibrosis

Karyopharm Therapeutics has submitted a supplemental new drug application (sNDA) to the FDA seeking accelerated approval for selinexor (Xpovio) in combination with ruxolitinib (Jakafi) for patients with myelofibrosis, according to a news release from the company.¹

The company also requested priority review, which, if granted, could result in a 6-month review process. The submission is based in part on data from the phase 3 SENTRY trial (NCT04562389), which the company believes supports a positive benefit-risk profile for the combination, including a promising overall survival (OS) signal.

What supports the selinexor sNDA in myelofibrosis?

The sNDA was submitted under the accelerated approval pathway based in part on SENTRY data that developers said support a positive benefit-risk profile, including rapid, deep, and sustained spleen responses; a promising OS signal; and evidence of disease modification. Accelerated approval would require the FDA to agree that a spleen volume reduction of 35% or greater (SVR35) is a reasonably likely surrogate end point to predict OS. Developers plan to use long-term OS data from SENTRY to verify clinical benefit and support conversion from accelerated to traditional approval.

“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 [have] a significant unmet need. 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 [OS] signal and important evidence of disease modification,” said Reshma Rangwala, MD, PhD, chief medical officer and head of research of Karyopharm, in the press release.¹ “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.”

What is the SENTRY trial design?

SENTRY is a phase 3 trial evaluating once-weekly selinexor at 60 mg in combination with ruxolitinib compared with placebo plus ruxolitinib in patients with JAK inhibitor–naive myelofibrosis and platelet counts greater than 100 x 10⁹/L (n = 353).² Patients were randomly assigned 2:1 to the selinexor or placebo arms.

The coprimary end points were SVR35 at week 24 and the average change in absolute total symptom score over 24 weeks relative to baseline. Results from SENTRY were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the Journal of Clinical Oncology, showing that selinexor plus ruxolitinib significantly improved spleen responses vs ruxolitinib alone with a manageable safety profile.²

What are selinexor and ruxolitinib?

Selinexor is a first-in-class, oral exportin 1 (XPO1) inhibitor that functions by selectively binding to and inhibiting the nuclear export protein XPO1; it is approved in the US in combination regimens for patients with multiple myeloma. Ruxolitinib is a JAK inhibitor, the only approved class of therapies for myelofibrosis, a rare blood cancer that causes bone marrow fibrosis, splenomegaly, and progressive anemia and affects approximately 20,000 patients in the US.

What is selinexor's regulatory history in myelofibrosis?

According to the press release, the FDA granted selinexor orphan drug designation for myelofibrosis in May 2022, and the European Commission granted orphan medicinal product designation in October 2022. In July 2023, the FDA granted fast track designation to selinexor for myelofibrosis, including primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis.³

Karyopharm expects to receive notice of the FDA’s decision on sNDA filing acceptance, and anticipated review timelines, in the fourth quarter of 2026 following the agency’s 60-day filing review period.

References

1. Karyopharm submits supplemental new drug application to the FDA for Xpovio (selinexor) plus ruxolitinib for patients with myelofibrosis. News release. Karyopharm Therapeutics Inc. August 31, 2026. Accessed September 1, 2026. https://tinyurl.com/ynpfv7pa
2. Mascarenhas J, Ali H, Al-Ali HK, et al. Selinexor plus ruxolitinib in JAK inhibitor–naïve myelofibrosis: phase 3 SENTRY trial. J Clin Oncol. 2026;44(suppl 17):LBA6500. doi:10.1200/JCO.2026.44.17_suppl.LBA6500
3. Karyopharm receives FDA fast track designation for selinexor for the treatment of myelofibrosis. News release. Karyopharm Therapeutics Inc. July 17, 2023. Accessed September 1, 2026. https://tinyurl.com/59xhcwkk