Newton, Massachusetts, August 31, 2026
Karyopharm Therapeutics Inc. announced the submission of a Supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking approval for XPOVIO® (selinexor) in combination with ruxolitinib for the treatment of patients with myelofibrosis. The regulatory submission is supported by data from the Phase 3 SENTRY clinical trial, which evaluated the investigational combination in patients with myelofibrosis who had not previously received a JAK inhibitor. If approved, the combination could provide a new treatment approach for patients with this chronic and potentially serious myeloproliferative neoplasm.
Phase 3 SENTRY Trial Supports FDA Submission
The sNDA is based on results from the SENTRY Phase 3 study, a randomized clinical trial designed to evaluate the efficacy and safety of selinexor in combination with ruxolitinib compared with ruxolitinib alone. The study focused on patients with previously untreated myelofibrosis, an important population because disease-associated symptoms, splenomegaly and abnormal blood counts can significantly affect patients’ quality of life and clinical outcomes. The investigational combination is designed to build on the activity of ruxolitinib, a Janus kinase (JAK) inhibitor commonly used in myelofibrosis treatment. Selinexor works through a different biological mechanism by inhibiting exportin 1 (XPO1), a nuclear export protein involved in the transport of proteins and RNA from the cell nucleus. By combining agents with distinct mechanisms, the development program is evaluating whether XPO1 inhibition can enhance the clinical effects of JAK inhibition in myelofibrosis. The SENTRY program assessed clinically relevant measures including spleen volume reduction and symptom response, which are important treatment goals in myelofibrosis. Reduction in enlarged spleen size and improvement in disease-related symptoms can be meaningful indicators of therapeutic benefit, particularly for patients experiencing abdominal discomfort, early satiety, fatigue and other manifestations of the disease.
Selinexor Targets XPO1 in Myelofibrosis
XPOVIO (selinexor) is an oral selective inhibitor of nuclear export, or SINE, compound. By targeting XPO1, selinexor is designed to interfere with the abnormal movement of proteins between the nucleus and cytoplasm. XPO1 plays a role in the transport of tumor suppressor proteins and other regulatory molecules, making the pathway a potential therapeutic target in several hematologic malignancies. The proposed combination with ruxolitinib reflects Karyopharm’s strategy of investigating selinexor in additional hematologic diseases and treatment settings. Myelofibrosis is characterized by abnormal blood-cell production and progressive scarring of the bone marrow, with patients potentially developing anemia, constitutional symptoms, splenomegaly and other complications. Treatment selection can be challenging, particularly as disease biology and treatment response vary among patients.Karyopharm’s regulatory filing therefore represents a significant development milestone for the selinexor clinical program. The company is seeking to expand the potential use of an established XPO1-targeting therapy into a combination regimen designed specifically for patients with myelofibrosis.
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FDA Review Will Determine Next Development Step
The submission of the sNDA does not constitute FDA approval. The regulatory agency will review the submitted clinical, safety and manufacturing information before determining whether the proposed selinexor and ruxolitinib combination meets the requirements for approval. The outcome of the FDA review will determine whether the regimen can become an additional treatment option for patients with myelofibrosis in the United States. The regulatory application highlights the continuing development of targeted treatment strategies for myelofibrosis, where researchers are investigating approaches that can address multiple aspects of the disease, including spleen enlargement and symptom burden. Combining therapies with complementary mechanisms is one strategy being evaluated to potentially improve treatment responses while maintaining an acceptable safety profile. For Karyopharm, the sNDA submission marks a key step in advancing XPOVIO plus ruxolitinib toward a potential new indication. The FDA’s assessment of the SENTRY clinical data will be closely watched by the hematology and oncology communities as the company seeks to determine whether the combination can expand therapeutic options for patients with previously untreated myelofibrosis.
Source: Karyopharm Therapeutics press relese
