Karyopharm's Phase 3 SENTRY Trial in Myelofibrosis Met First Co-Primary Endpoint

Karyopharm Therapeutics Inc. reported topline results from its Phase 3 SENTRY trial. The randomized, double-blind, placebo-controlled study tested 60 milligrams of selinexor once weekly plus ruxolitinib against placebo plus ruxolitinib in 353 patients with frontline myelofibrosis. The trial met its first co-primary endpoint. Fifty percent of patients on the combination achieved a spleen volume reduction of 35 percent or more at week 24, compared with 28 percent on ruxolitinib alone. The difference reached statistical significance with a one-sided p value below 0.0001. Spleen volume reduction developed rapidly and was sustained in the combination arm. Forty-nine percent of patients reached the threshold at week 12 versus 20 percent on ruxolitinib alone. Forty-seven percent maintained the response at week 36 versus 23 percent. Symptom scores improved to a similar degree in both arms. Patients on the combination recorded a 9.89 point gain in absolute total symptom score at week 24, compared with a 10.86 point gain for ruxolitinib alone. The between-arm difference was not statistically significant. A promising overall survival signal emerged. The hazard ratio favored the combination at 0.43 with a nominal one-sided p value of 0.0222. Post-hoc analyses suggested that achieving the spleen volume endpoint may predict survival. Variant allele frequency reductions provided evidence of potential disease modification. Thirty-two percent of combination patients reached at least a 20 percent drop at week 24 versus 24 percent on ruxolitinib alone. The combination maintained a manageable safety profile. No new safety signals appeared. The most common adverse events included thrombocytopenia, anemia, and nausea, with higher rates of some events in the combination arm. Karyopharm will meet with the U.S. Food and Drug Administration to review the full data set and discuss a potential supplemental new drug application. The company scheduled a conference call for 8 a.m. Eastern time on the day of the announcement.