Karyopharm Therapeutics has announced plans to submit a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) in August 2026, seeking accelerated approval for selinexor in combination with ruxolitinib for the treatment of patients with myelofibrosis, a rare and debilitating blood cancer.

The planned submission follows discussions with the FDA, during which the agency indicated that achieving 35 percent or greater spleen volume reduction (SVR35) appears to be a reasonably likely surrogate endpoint capable of predicting overall survival, making it suitable to support an application under the accelerated approval pathway.

To confirm long-term clinical benefit, Karyopharm intends to rely on overall survival data from the ongoing Phase 3 SENTRY trial, where overall survival is a pre-specified secondary endpoint. The study remains blinded, with no patient crossover permitted, allowing continued unbiased assessment of treatment outcomes.

If approved, the combination of selinexor and ruxolitinib would become the first approved combination therapy for myelofibrosis, introducing a novel treatment class for patients who currently rely primarily on JAK inhibitor therapy.

The sNDA will be supported by results from the randomised, double-blind Phase 3 SENTRY trial, which compared selinexor plus ruxolitinib with placebo plus ruxolitinib in previously untreated, JAK inhibitor-naïve patients with myelofibrosis.

The study demonstrated a statistically significant improvement in spleen volume reduction at Week 24, along with rapid, deep and sustained spleen responses. Investigators also reported encouraging signals for overall survival, reductions in variant allele frequency—suggesting potential disease modification—and a favourable overall safety profile.

Karyopharm also plans to request Priority Review for the application. If granted, the FDA is expected to issue a decision approximately six months after accepting the filing under the Prescription Drug User Fee Act (PDUFA) timeline.

The SENTRY trial enrolled 353 JAK inhibitor-naïve patients with platelet counts above 100 × 10?/L, who were randomized in a 2:1 ratio to receive either once-weekly 60 mg selinexor plus ruxolitinib or placebo plus ruxolitinib. The study's co-primary endpoints include achieving SVR35 at Week 24 and improvement in total symptom score over 24 weeks.

Results from the trial were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, simultaneously published in the Journal of Clinical Oncology, and later featured at the 2026 European Hematology Association (EHA) Congress, where the presentation was recognised among the conference's six best abstracts.

Myelofibrosis affects an estimated 20,000 patients in the United States and 17,000 patients across the European Union. The disease causes progressive scarring of the bone marrow, enlarged spleen, anaemia and debilitating symptoms including fatigue, abdominal discomfort, early satiety, night sweats and bone pain. Current approved treatments are primarily limited to JAK inhibitors, highlighting the need for innovative therapeutic options.