Karyopharm Therapeutics Inc, a commercial-stage pharmaceutical company pioneering novel cancer therapies, announced that it plans to submit a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) in August 2026 seeking accelerated approval of selinexor in combination with ruxolitinib for the treatment of patients with myelofibrosis.
The planned submission follows productive engagements with the US FDA, including written feedback that spleen volume reduction = 35% (SVR35) appears to qualify as a reasonably likely surrogate endpoint (RLSE) to predict overall survival and can be used to support an sNDA under the accelerated approval pathway. The company plans to use overall survival data from long-term follow-up of the ongoing phase 3 SENTRY trial to verify clinical benefit. Overall survival is a pre-specified secondary endpoint of SENTRY. The trial does not permit patient crossover; patients, investigators and the Karyopharm study team remain blinded to treatment assignment during ongoing follow-up.
If approved, selinexor in combination with ruxolitinib has the potential to become the first approved combination therapy for patients with myelofibrosis, adding a novel class of therapy.
"The SENTRY trial generated one of the most compelling frontline datasets in myelofibrosis to date," said Dr. John Mascarenhas, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and director of the Center of Excellence for Blood Cancers and Myeloid Disorders. "The combination of selinexor and ruxolitinib demonstrated compelling spleen responses across a broad range of subgroups. The spleen responses were rapid, deep and sustained with promising overall survival findings and important evidence of disease modification. These results have the potential to redefine frontline treatment and establish a new treatment paradigm for patients with myelofibrosis."
"Patients with myelofibrosis have waited too long for meaningful innovation," said Richard Paulson, President and chief executive officer of Karyopharm. "We are grateful to the US FDA for its thoughtful and collaborative engagement in helping define a rigorous path forward. If approved, selinexor in combination with ruxolitinib has the potential to become the first approved combination therapy for patients with myelofibrosis, incorporating a novel class of therapy. We believe this represents a potentially transformative opportunity for patients and a defining moment in Karyopharm's history as we work with urgency toward our planned August sNDA submission."
The planned sNDA will be based on results from the randomized, double-blind, phase 3 SENTRY trial that compared selinexor in combination with ruxolitinib against placebo in combination with ruxolitinib, including the statistically significant improvement in SVR35 at week 24, the rapid, deep and sustained nature of the spleen responses, a promising overall survival signal, reductions in variant allele frequency and the overall safety data package.
"The SENTRY trial generated a substantial body of evidence showing consistent improvements across multiple measures of clinical activity, including spleen response and a promising signal of overall survival," said Reshma Rangwala, chief medical officer and head of research of Karyopharm. "Together, these findings reinforce the biologic rationale for combining XPO1 and JAK inhibition and support the potential of this novel combination to deliver meaningful long-term benefits for patients with myelofibrosis."
Karyopharm intends to request Priority Review at the time of submission of the sNDA, which, if granted, would result in a Prescription Drug User Fee Act (PDUFA) target action date approximately six months following the FDA's receipt of the application.
SENTRY is a phase 3 clinical trial evaluating a once-weekly dose of 60 mg of selinexor in combination with ruxolitinib compared to placebo plus ruxolitinib in JAKi-naïve myelofibrosis patients with platelet counts >100 x 109/L (N=353). Patients were randomized 2-to-1 to the selinexor arm. The co-primary endpoints for this trial are spleen volume reduction = 35% (SVR35) at week 24 and the average change in absolute total symptom score (Abs-TSS) over 24 weeks relative to baseline. The results from the phase 3 SENTRY trial were presented at the 2026 American Society of Clinical Oncology Annual Meeting and were simultaneously published in the peer-reviewed Journal of Clinical Oncology. In addition, the results were presented at the 2026 European Hematology Association Congress, where the presentation was recognized as one of the six best abstracts at the meeting.
Myelofibrosis is a rare blood cancer that affects approximately 20,000 patients in the United States and 17,000 patients in the European Union. The disease causes bone marrow fibrosis (scarring in the bone marrow), which makes it difficult for the bone marrow to make healthy blood cells, splenomegaly (enlarged spleen), progressive anaemia which often leads to symptoms like fatigue and weakness, and other disease associated symptoms including abdominal discomfort, pain under the left ribs, early satiety, night sweats and bone pain. The only approved class of therapies to treat myelofibrosis are JAK inhibitors, including ruxolitinib. |