Karyopharm Seeks FDA Approval for XPOVIO Plus Ruxolitinib in Myelofibrosis

Karyopharm Therapeutics announced that it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for XPOVIO (selinexor) in combination with ruxolitinib for patients with myelofibrosis.

The company also requested Priority Review, which could shorten the FDA's review timeline to six months if the designation is granted. The FDA's Priority Review goal is to take action on an application within six months, compared with 10 months for a standard review.

The application is based in part on findings from the phase 3 SENTRY trial, which evaluated XPOVIO plus ruxolitinib compared with ruxolitinib alone in patients with myelofibrosis who had not previously received a JAK inhibitor.

What Did the SENTRY Trial Find?

The SENTRY trial included 353 patients who were randomly assigned to receive either XPOVIO plus ruxolitinib or placebo plus ruxolitinib. The trial's co-primary endpoints were a reduction in spleen volume of at least 35% at week 24 and a change in patients' total symptom scores.

At week 24, 49.8% of patients who received XPOVIO plus ruxolitinib experienced at least a 35% reduction in spleen volume, compared with 28% of patients who received ruxolitinib alone. The difference was statistically significant.

The reduction in spleen volume was observed early in treatment and remained evident through week 36. Researchers reported that the average spleen volume decreased by 40% in the XPOVIO-plus-ruxolitinib group at week 24, compared with a 26.7% reduction in the ruxolitinib-alone group.

However, the combination did not meet the second co-primary endpoint evaluating improvement in symptoms. Although symptoms improved from baseline in both treatment groups, there was no statistically significant difference between the groups.

The trial also showed an early overall survival signal. After approximately 12 months of follow-up, the overall survival hazard ratio was 0.43, although longer-term follow-up will be needed to better understand the potential survival benefit.

What Is Myelofibrosis?

Myelofibrosis is a rare blood cancer that causes scarring, or fibrosis, in the bone marrow. As the disease progresses, the bone marrow can have difficulty producing healthy blood cells.

The disease can also cause an enlarged spleen, anemia and symptoms such as fatigue, weakness, abdominal discomfort, pain beneath the left ribs, feeling full after eating only a small amount, night sweats and bone pain.

Ruxolitinib, a JAK inhibitor, is one of the established treatments used to manage myelofibrosis. However, some patients may have inadequate or temporary responses, creating a need for additional treatment approaches.

What Would Accelerated Approval Mean?

Karyopharm is seeking accelerated approval based on spleen volume reduction of at least 35% as a surrogate endpoint that could be considered reasonably likely to predict overall survival.

The FDA's Accelerated Approval pathway can allow certain treatments for serious conditions to be approved based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Treatments approved through this pathway generally require additional studies after approval to confirm the expected clinical benefit.

Karyopharm said it plans to use longer-term overall survival data from the SENTRY trial to verify clinical benefit and support a potential transition from accelerated approval to traditional approval.

The company expects the FDA to notify it during the fourth quarter of 2026 whether the application has been accepted for review and, if accepted, provide the anticipated review timeline.

What Happens Next?

The FDA has not yet approved XPOVIO in combination with ruxolitinib for myelofibrosis. The submission begins the regulatory review process, and the FDA will determine whether the application is accepted and whether Priority Review is granted.

For patients and families, the potential approval would represent another treatment option for a disease in which controlling spleen enlargement, symptoms and the underlying disease remains an important treatment goal.

XPOVIO is already approved in the United States for certain patients with multiple myeloma. Its potential use in combination with ruxolitinib for myelofibrosis remains investigational unless and until the FDA grants approval.

References

1. “Karyopharm Submits Supplemental New Drug Application to the FDA for XPOVIO® (selinexor) Plus Ruxolitinib for Patients with Myelofibrosis.” Karyopharm Therapeutics Inc. August 31, 2026.

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