Karyopharm Therapeutics Inc. (NASDAQ:KPTI) saw its stock rise 10% on Tuesday after announcing mixed outcomes from the Phase 3 SENTRY trial assessing selinexor in combination with ruxolitinib in patients with newly diagnosed myelofibrosis.
The trial achieved one of its two co-primary endpoints. Patients receiving the combination therapy showed a statistically significant improvement in spleen volume reduction versus ruxolitinib with placebo. By week 24, 50% of patients treated with selinexor plus ruxolitinib reached a 35% or greater reduction in spleen volume (SVR35), compared with 28% of those on ruxolitinib alone.
However, the study did not meet its second co-primary endpoint, which measured symptom improvement. Both arms experienced similar reductions in symptom burden from baseline, and the observed difference between arms did not reach statistical significance. Patients in the combination arm reported a 9.89 point improvement in absolute total symptom score, while those on ruxolitinib alone reported a 10.86 point improvement.
Investigators noted an encouraging overall survival signal in the dataset. The combination arm demonstrated a hazard ratio of 0.43 compared with ruxolitinib alone; Karyopharm said it will continue follow-up until overall survival data reach maturity.
Exploratory analyses provided additional context on potential disease modification. At week 24, 32% of patients in the combination arm achieved a 20% or greater reduction in variant allele frequency, versus 24% in the ruxolitinib-alone arm.
Safety findings were described as manageable, with no new safety signals identified. The most frequently reported adverse events in the selinexor plus ruxolitinib arm were thrombocytopenia (59%), anemia (57%), and nausea (57%).
Looking ahead, Karyopharm said it intends to engage the U.S. Food and Drug Administration to review the SENTRY data and discuss a potential supplemental new drug application filing. In parallel, the company announced a private placement with RA Capital Management that is expected to generate approximately $30 million in gross proceeds.
Context and next steps
The SENTRY trial's mixed readout leaves clear regulatory and clinical questions to resolve. Karyopharm's plan to consult with the FDA and continue overall survival follow-up reflects the company’s intent to clarify the regulatory path based on the totality of the data. The announced private placement will provide additional near-term liquidity as the company advances those discussions.