Karyopharm changes endpoint in Phase 3 trial of selinexor in myelofibrosis

Karyopharm (KPTI) announced that, following feedback from the FDA, the company will be replacing Total Symptom Score Improvement of greater than or equal to 50%, or TSS50, one of the co-primary endpoints in the Phase 3 SENTRY Trial, with Absolute Total Symptom Score, or Abs-TSS. Abs-TSS measures the average improvement in patient symptom scores over 24 weeks relative to the patient’s baseline symptom score. Data from the company’s Phase 1 trial, evaluating the combination of selinexor 60mg plus ruxolitinib in JAKi naive myelofibrosis patients, demonstrated that 79% of patients in the intent to treat population achieved SVR35 and an average Abs-TSS improvement of 18.5 points in the efficacy evaluable population at week 24 relative to baseline. The safety profile remains consistent and no new safety signals have been identified. Based upon enrollment, the trial remains on track to report top-line results in the second half of 2025. Abs-TSS is an accepted measure that has been used in other Phase 3 clinical trials in myelofibrosis to evaluate the benefit/risk of an add-on treatment, such as selinexor, to the current standard of care. The change to Abs-TSS is supported by leading investigators and patient advocacy organizations.