NEWTON, Mass., July 30, 2026
Karyopharm Therapeutics Inc. plans to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) in August 2026 seeking accelerated approval of selinexor in combination with ruxolitinib for patients with myelofibrosis, marking an important regulatory step for the company’s oncology portfolio. The planned application follows discussions with the FDA indicating that spleen volume reduction of at least 35% (SVR35) appears to qualify as a reasonably likely surrogate endpoint for predicting overall survival and could support an application through the accelerated approval pathway. Karyopharm also intends to request Priority Review when the sNDA is submitted. If approved, the combination could become the first approved combination therapy for patients with myelofibrosis incorporating a novel class of therapy, potentially establishing a new frontline treatment option for this rare blood cancer.
FDA Engagement Defines Accelerated Approval Pathway
Karyopharm’s planned regulatory submission follows FDA feedback regarding the clinical evidence required to pursue accelerated approval for the selinexor-ruxolitinib combination. The company said the FDA indicated that SVR35 may serve as a reasonably likely surrogate endpoint for overall survival, providing a potential regulatory pathway based on results from the company’s pivotal Phase 3 SENTRY trial. Karyopharm plans to supplement the accelerated approval package with long-term overall survival data from the ongoing SENTRY study to verify clinical benefit. Overall survival is a prespecified secondary endpoint of the trial, and importantly, the study does not permit patient crossover while patients, investigators and the Karyopharm study team remain blinded during continued follow-up. The company plans to submit the sNDA in August 2026 and request Priority Review, which, if granted, could result in a PDUFA target action date approximately six months after FDA receipt of the application.
Phase 3 SENTRY Data Support Selinexor Combination
The planned sNDA will be supported by results from the randomized, double-blind Phase 3 SENTRY trial, which compared once-weekly 60 mg selinexor plus ruxolitinib against placebo plus ruxolitinib in 353 JAK inhibitor-naïve patients with myelofibrosis. The study demonstrated a statistically significant improvement in SVR35 at Week 24, alongside rapid, deep and sustained spleen responses. Karyopharm also reported a promising overall survival signal, reductions in variant allele frequency and an overall safety data package supporting the planned regulatory filing. The trial’s co-primary endpoints include spleen volume reduction of at least 35% at Week 24 and average change in absolute total symptom score over 24 weeks relative to baseline. The findings were presented at the 2026 American Society of Clinical Oncology Annual Meeting and published in the Journal of Clinical Oncology, with additional results presented at the 2026 European Hematology Association Congress.
Advertisement
Novel XPO1 and JAK Inhibition Could Shift Myelofibrosis Care
Myelofibrosis is a rare blood cancer characterized by progressive bone marrow fibrosis that disrupts normal blood cell production and can result in splenomegaly, anemia, fatigue, weakness, night sweats, bone pain and abdominal symptoms. Approximately 20,000 patients in the United States and 17,000 in the European Union are affected by the disease. Currently, the only approved therapeutic class for myelofibrosis is JAK inhibitors, including ruxolitinib. Selinexor, marketed as XPOVIO® for approved multiple myeloma indications, is a first-in-class oral exportin 1 (XPO1) inhibitor that selectively blocks the nuclear export protein XPO1. Combining XPO1 inhibition with JAK inhibition introduces a distinct therapeutic strategy that Karyopharm believes could provide deeper and more durable clinical benefits. If the planned sNDA ultimately receives FDA approval, the combination could expand frontline treatment choices and potentially establish a new therapeutic paradigm for patients with myelofibrosis.
Source: Karyopharm Therapeutics press release
