"Today's submission is an important step toward our goal of bringing the combination of selinexor plus ruxolitinib to patients with myelofibrosis who continue to face a significant unmet need," said Reshma Rangwala, M.D., Ph.D., Chief Medical Officer and Head of Research of Karyopharm. "The SENTRY trial generated compelling and consistent results, including rapid, deep and sustained spleen responses across a broad range of patients, together with a promising overall survival signal and important evidence of disease modification. We believe the strength of these data underscores the potential of this novel combination to deliver meaningful long-term benefits and fundamentally change the treatment of patients with myelofibrosis."
Following the topline results of the Phase 3 SENTRY trial, the Company has engaged productively with the FDA. The sNDA submitted is based, in part, on data from the SENTRY trial that the Company believes supports a positive benefit-risk profile for the combination, including a promising signal of overall survival. The Company expects approval under the Accelerated Approval pathway would require the FDA to agree that spleen volume reduction ≥ 35% (SVR35) is a reasonably likely surrogate endpoint to predict overall survival.
The Company plans to use long-term overall survival data from the Phase 3 SENTRY trial to verify clinical benefit and support conversion from accelerated to traditional approval and expects to continue working with the FDA during its review of the sNDA to finalize the confirmatory evidence plan. Karyopharm expects to receive notice of the FDA's decision on sNDA filing acceptance and, if accepted, the anticipated review timelines in the fourth quarter of 2026, following the FDA's 60-day filing review period.
In May 2022, the FDA granted selinexor Orphan Drug Designation for the treatment of myelofibrosis, and in October 2022, the European Commission granted Orphan Medicinal Product Designation for selinexor for the treatment of myelofibrosis. In addition, in July 2023, the Company received Fast Track Designation from the FDA for selinexor for the treatment of patients with myelofibrosis, including primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis.
About the Phase 3 SENTRY Trial
SENTRY (XPORT-MF-034; NCT04562389) 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.
About Myelofibrosis
Myelofibrosis is a rare blood cancer that affects approximately 20,000 patients in the United States and 19,000 patients in the European Union1. 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 anemia 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.
About XPOVIO® (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor compound for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved and marketed by Karyopharm in the U.S. in multiple oncology indications, including: (i) in combination with VELCADE® (bortezomib) and dexamethasone (XVd) in adult patients with multiple myeloma after at least one prior therapy; and (ii) in combination with dexamethasone in adult patients with heavily pre-treated multiple myeloma. XPOVIO® (also known as NEXPOVIO® in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, Mainland China, Taiwan, Hong Kong, Australia, South Korea, Singapore, Israel, and Canada. XPOVIO®/NEXPOVIO® is marketed in these respective ex-U.S. territories by Karyopharm's partners: Antengene, Menarini, Neopharm, and FORUS. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high-unmet need cancer indications.
About Karyopharm Therapeutics
Karyopharm Therapeutics is a commercial-stage pharmaceutical company pioneering the science of nuclear export inhibition to develop differentiated therapies for patients with cancer. The Company's lead therapy, XPOVIO® (selinexor), is a first-in-class inhibitor of exportin 1 (XPO1). XPOVIO is marketed by the Company in the U.S. for adults with relapsed or refractory multiple myeloma and is approved as XPOVIO or NEXPOVIO® in more than 50 ex-U.S. countries and territories. Building on its leadership in XPO1 biology, Karyopharm is advancing selinexor's potential in hematological cancers, including in myelofibrosis. The Company is also exploring opportunities to evaluate XPO1 inhibition across myeloproliferative neoplasms using next-generation compounds, including eltanexor. Headquartered in Newton, Massachusetts, Karyopharm has an established, efficient, and scalable commercial infrastructure to bring novel therapeutic options to patients with cancer.
For more information, visit www.karyopharm.com
