Karyopharm Prepares for Pivotal 2026 with Phase 3 Myelofibrosis Data Expected in March
核心洞察
Karyopharm expects top-line data from its Phase 3 SENTRY trial evaluating selinexor plus ruxolitinib in myelofibrosis (搜索) patients in March 2026, potentially unlocking the first combination therapy in this multi-billion dollar market.
The company also anticipates mid-2026 results from its Phase 3 XPORT-EC-042 trial in endometrial cancer (搜索), representing another significant opportunity for patient outcomes in a targeted population.
Preliminary 2025 revenue reached approximately $145 million total and $115 million in U.S. XPOVIO net product sales, with cash runway extending beyond the expected SENTRY trial readout.
Karyopharm Therapeutics is positioning 2026 as a potentially transformative year with two critical Phase 3 data readouts that could significantly expand the commercial potential of its flagship drug XPOVIO (selinexor). The company announced preliminary unaudited 2025 revenue figures while outlining key clinical milestones expected throughout 2026.
Phase 3 SENTRY Trial Poised for March 2026 Readout
The most anticipated catalyst is top-line data from the Phase 3 SENTRY trial in myelofibrosis (搜索), expected in March 2026. The study completed enrollment in early September 2025 with 353 patients, evaluating 60 mg once-weekly selinexor in combination with ruxolitinib compared to ruxolitinib plus placebo in JAK inhibitor-naïve patients.
"Positive data from our SENTRY trial could unlock our opportunity to improve patient outcomes and redefine the standard-of-care in myelofibrosis (搜索)," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "Our teams are actively preparing for regulatory filings, commercialization and the opportunity to rapidly launch with the first ever combination therapy in a multi-billion dollar market."
The trial's co-primary endpoints are spleen volume reduction ≥35% at week 24 and the average change in absolute total symptom score over 24 weeks relative to baseline. Preliminary baseline characteristics presented at the American Society of Hematology 2025 Annual Meeting showed the enrolled population (n=320) was representative of the intended patient population.
Preliminary blinded aggregate safety data from the first 61 patients with median follow-up greater than 12 months suggested potential improvements in both hematologic and non-hematologic treatment emergent adverse events compared to Phase 1 data and historical ruxolitinib monotherapy data, though the company cautioned these preliminary results may not reflect actual trial outcomes.
Addressing Significant Unmet Need in Myelofibrosis
Myelofibrosis (搜索) affects approximately 20,000 patients in the United States and 17,000 patients in the European Union. The disease causes bone marrow fibrosis, making it difficult for bone marrow to produce healthy blood cells, leading to splenomegaly, progressive anemia, fatigue, weakness, and other debilitating symptoms.
Currently, JAK inhibitors including ruxolitinib represent the only approved class of therapies for myelofibrosis (搜索). However, patients treated with the most commonly prescribed JAK inhibitor often require blood transfusions, and more than 30% discontinue treatment due to anemia. Anemia and transfusion dependence correlate with poor prognosis and shortened survival.
Endometrial Cancer Trial Targets Mid-2026 Results
The company also expects top-line data from its Phase 3 XPORT-EC-042 trial in endometrial cancer (搜索) in mid-2026. This event-driven trial is evaluating selinexor as maintenance therapy following systemic therapy versus placebo in patients with TP53 (搜索) wild-type advanced or recurrent endometrial cancer.
The trial design was modified to focus enrollment on patients with either proficient mismatch repair status (pMMR) tumors or patients with deficient mismatch repair status (dMMR) tumors who are medically ineligible for checkpoint inhibitors. The modified intent-to-treat population includes approximately 220 patients, with the total ITT sample size increased to approximately 276 patients.
Endometrial cancer (搜索) represents the most common gynecologic malignancy in the U.S., with approximately 69,120 uterine cancers expected to be diagnosed in 2025 and 13,860 deaths. More than 50% of advanced or recurrent endometrial cancer tumors are TP53 (搜索) wild-type, and approximately 40%-55% are both TP53 wild-type and mismatch repair-proficient, representing a significant patient population with unmet therapeutic needs.
Commercial Performance and Financial Position
XPOVIO demonstrated consistent demand in 2025 versus 2024 in the increasingly competitive multiple myeloma (搜索) marketplace, with the community setting continuing to drive approximately 60% of overall net product revenue. Global patient access expanded with favorable reimbursement decisions in Spain and China, and additional regulatory approvals bringing the total to more than 50 countries.
Based on preliminary unaudited financial information, Karyopharm expects total revenue of approximately $145 million for full year 2025, with U.S. XPOVIO net product revenue of approximately $115 million. Fourth quarter 2025 total revenue is expected to be approximately $33 million, with U.S. XPOVIO net product revenue of approximately $32 million.
The company reported cash, cash equivalents, restricted cash and investments of approximately $64 million as of December 31, 2025. Combined with expected revenue from XPOVIO sales and license agreements, this liquidity is projected to fund planned operations into the second quarter of 2026, extending beyond the expected SENTRY trial readout.
Additional Pipeline Developments
Beyond the two pivotal Phase 3 trials, Karyopharm continues advancing its selinexor development program across multiple indications. The company expects to report top-line data from all patients in the 60 mg cohort of the Phase 2 SENTRY-2 trial with at least 24 weeks of follow-up in the second half of 2026.
In multiple myeloma (搜索), the company continues following patients enrolled in the Phase 3 XPORT-MM-031 (EMN29) trial, with top-line data from this event-driven trial expected in the second half of 2026.
XPOVIO represents a first-in-class oral exportin 1 (XPO1 (搜索)) inhibitor that functions by selectively binding to and inhibiting the nuclear export protein XPO1. The drug is currently approved in the U.S. for multiple oncology indications, including combination therapy with bortezomib and dexamethasone in multiple myeloma (搜索) patients after at least one prior therapy, and has received regulatory approvals in various indications across more than 50 ex-U.S. territories and countries.