On July 30, 2026 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that it 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 the treatment of patients with myelofibrosis.
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The planned submission follows productive engagements with the 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.
"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 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, M.D., Ph.D., 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.
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 (ASCO) (Free ASCO Whitepaper) 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 (EHA) (Free EHA Whitepaper) 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 17,000 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.
1. Clarivate/DRG (2023)
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.
For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: [email protected]
XPOVIO (selinexor) is a prescription medicine approved:
In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd).
SELECT IMPORTANT SAFETY INFORMATION
Warnings and Precautions
Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
Use In Specific Populations
Lactation: Advise not to breastfeed.
For additional product information, including full prescribing information, please visit www.XPOVIO.com.
To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.
(Press release, Karyopharm, JUL 30, 2026, View Source [SID1234669536])