Karyopharm Therapeutics has submitted an application to the FDA seeking accelerated approval for selinexor plus ruxolitinib in myelofibrosis.

Application follows Phase 3 SENTRY results

The supplemental New Drug Application (sNDA) seeks approval of XPOVIO (selinexor) in combination with ruxolitinib for patients with myelofibrosis.

Karyopharm has also requested Priority Review, which, if granted, could lead to a six-month FDA review.

The application is partly supported by results from the Phase 3 SENTRY trial, which evaluated once-weekly selinexor in combination with ruxolitinib in patients with myelofibrosis who had not previously received a JAK inhibitor.

The trial enrolled 353 patients, who were randomised in a 2-to-1 ratio to receive selinexor plus ruxolitinib or placebo plus ruxolitinib.

The study had two co-primary endpoints: spleen volume reduction of at least 35% at week 24 and the average change in absolute total symptom score over 24 weeks compared with baseline.

Karyopharm said the data also showed a signal for overall survival, alongside evidence that the treatment combination could modify disease progression.

Reshma Rangwala, chief medical officer and head of research at Karyopharm, said: “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.”

FDA accelerated approval pathway

The company is seeking accelerated approval based on spleen volume reduction of at least 35% as a potential surrogate endpoint.

For accelerated approval to be granted, the FDA would need to agree that the reduction in spleen volume is reasonably likely to predict clinical benefit, including overall survival.

Karyopharm plans to use longer-term overall survival data from SENTRY to verify clinical benefit and support conversion from accelerated to traditional approval.

The company expects to continue discussions with the FDA during the review to finalise the confirmatory evidence plan.

Karyopharm expects the FDA to provide a decision on whether the sNDA has been accepted for filing during the fourth quarter of 2026, following the agency’s 60-day filing review period.

Myelofibrosis treatment

Myelofibrosis is a rare blood cancer in which fibrosis, or scarring, develops in the bone marrow and affects the production of healthy blood cells.

The disease can cause an enlarged spleen, anaemia, fatigue, weakness, abdominal discomfort, night sweats and bone pain.

Ruxolitinib is a JAK inhibitor and is among the treatments currently used for myelofibrosis.

Selinexor is an oral inhibitor of exportin 1, a protein involved in transporting molecules out of the cell nucleus. XPOVIO is already approved in the US in combination with other medicines for certain patients with multiple myeloma.

The SENTRY results were presented at the 2026 American Society of Clinical Oncology Annual Meeting and published in the Journal of Clinical Oncology. They were also presented at the 2026 European Hematology Association Congress.