Karyopharm Therapeutics Teases ASCO SENTRY Data as FDA Path Comes Into Focus

Key Points

• Karyopharm said it will present fuller Phase 3 SENTRY data for selinexor in newly diagnosed myelofibrosis at ASCO, including efficacy, safety and disease-modification measures. The company previously reported “rapid, deep, and sustained” spleen volume responses and a promising overall survival signal.
• The company expects to engage the FDA over the next one to two quarters on the regulatory path for selinexor in myelofibrosis, and it is also hoping for NCCN guideline inclusion. Management said both an ASCO presentation and a peer-reviewed publication could support broader adoption and payer coverage.
• Karyopharm highlighted two other growth areas: an upcoming endometrial cancer Phase 3 readout focused on progression-free survival, and longer-term development of eltanexor, its second-generation XPO1 inhibitor. The company sees both myelofibrosis and endometrial cancer as large, under-served markets.

Karyopharm Therapeutics NASDAQ: KPTI executives said the company expects to provide a fuller presentation of its Phase 3 SENTRY trial data for selinexor in myelofibrosis at the upcoming ASCO conference, while also outlining expected regulatory engagement and other development priorities during a recent company event.

President and CEO Richard Paulson and Chief Medical Officer Reshma Rangwala discussed the company’s late-breaker ASCO presentation for SENTRY, a Phase 3 study evaluating selinexor plus ruxolitinib in newly diagnosed myelofibrosis patients with baseline platelet counts above 100. Rangwala said the ASCO presentation will be the first public medical-congress presentation of the data and is expected to cover clinical endpoints, safety and disease-modification measures.

SENTRY Data to Be Presented at ASCO

Rangwala said the previously announced topline results showed “rapid, deep, and sustained” SVR35, meaningful improvements in total symptom score at week 24 relative to baseline, and a “promising overall survival signal” at a median follow-up of about 12 months.

She said the company did not identify new safety signals and noted that selinexor is already an approved therapy with a recognized safety profile. Rangwala also highlighted the role of XPO1 inhibition, saying the mechanism is reflected in spleen volume reduction, variant allele frequency improvements and the observed survival signal.

According to Rangwala, the overall survival hazard ratio reported by the company was 0.43, with a nominal P value of 0.0222. She said the pattern of events was consistent with what would be expected, including progressive disease and toxicity, but said she did not want to provide further detail ahead of ASCO.

Rangwala said the data cutoff for the ASCO presentation was Feb. 20 and that the company does not plan another cutoff before the meeting. She added that the SENTRY study was designed to follow overall survival until maturity, with patients and physicians remaining blinded to treatment assignment.

Regulatory and Guideline Pathways

On the regulatory path, Rangwala said Karyopharm expects to gain and provide clarity on next steps with the U.S. Food and Drug Administration over the next one to two quarters, or within about six months if not earlier. She said the FDA division expected to review the program has been “remarkably stable” and was involved in agreeing to the Phase 3 trial design before SENTRY began.

Paulson also discussed the potential for inclusion in NCCN guidelines. He said the company has received positive feedback from opinion leaders and investigators regarding interest in having selinexor included in guidelines for myelofibrosis, and he pointed to the ASCO presentation and a planned peer-reviewed publication as important inputs.

Paulson said that in other examples where products already on the market generate new data in high-unmet-need settings, an NCCN listing can help products reach about 50% of their potential peak opportunity compared with a full label, while noting that such use would not be an area the company could actively promote.

He added that NCCN inclusion can support broad payer coverage, and said Karyopharm already has patient support, payer engagement and access capabilities in place.

Endometrial Cancer Study Remains a Key Data Event

The executives also discussed Karyopharm’s Phase 3 endometrial cancer maintenance study. Rangwala said progression-free survival is the primary endpoint, along with topline safety data, and said overall survival will continue to be followed.

Rangwala described the endometrial cancer treatment landscape as one where chemotherapy remains the “workhorse,” with checkpoint inhibitors such as dostarlimab and pembrolizumab now used with chemotherapy and continued into maintenance. She said checkpoint inhibitor efficacy is greatest in mismatch repair-deficient patients, who account for about 20% of endometrial cancer patients, while efficacy is more modest in the mismatch repair-proficient population.

She cited the RUBY trial’s exploratory post-hoc analysis in the p53 wild-type, pMMR subgroup, saying the hazard ratio of 0.77 highlighted modest efficacy in that group. Rangwala said Karyopharm’s earlier SIENDO data showed “substantially better efficacy” and that the goal of the XPORT-EC-042 trial is to demonstrate statistically significant and clinically meaningful progression-free survival outcomes.

Paulson said awareness of the SIENDO data is high among key opinion leaders, aided by multiple presentations over the past two to three years. He said molecular classification is now standard, including understanding p53 status, and that physicians want a medication that can act on that status.

Paulson characterized both endometrial cancer and myelofibrosis as multi-billion-dollar market opportunities with few treatment options compared with multiple myeloma. He said the endometrial cancer opportunity is focused on the p53 wild-type pMMR group, which he described as about 50% of patients.

Commercial Infrastructure and Myeloma Use

Discussing current multiple myeloma use, Paulson said about 60% of utilization is in the community setting and 40% in academic settings. He said selinexor is used primarily in the community in second- to fourth-line post-daratumumab settings, while academic use tends to occur around T-cell engaging therapies such as bispecifics and CAR-T.

Paulson said Karyopharm’s commercial capabilities could be leveraged across multiple myeloma, myelofibrosis and endometrial cancer because many patients are treated in the community and prescribing is concentrated among certain groups. He said targeted expansion could be considered for academic coverage, particularly in gynecologic oncology, if the company commercializes in endometrial cancer and myelofibrosis.

Eltanexor Development Considerations

Rangwala also discussed eltanexor, Karyopharm’s second-generation XPO1 inhibitor. She said it has the same target as selinexor but different properties, including a lower IC50 that may allow lower and more chronic dosing. She said eltanexor has already been evaluated in a Phase 1/2 trial across multiple solid tumors, multiple myeloma and myelodysplastic syndromes.

Rangwala said future development could include other myeloproliferative neoplasms such as polycythemia vera and essential thrombocythemia, as well as solid tumors where the company could leverage the p53 biomarker. Paulson said patent protection for eltanexor could start in the mid-2030s and potentially extend into the late 2030s, while selinexor’s polymorph patent extends to August 2035.

About Karyopharm Therapeutics NASDAQ: KPTI

Karyopharm Therapeutics NASDAQ: KPTI is a clinical-stage biopharmaceutical company focused on discovering and developing novel first-in-class drugs that target the nuclear export protein XPO1. The company's lead product, selinexor (marketed as XPOVIO), is an oral selective inhibitor of nuclear export (SINE) compound approved for treatment of multiple myeloma and diffuse large B-cell lymphoma. In addition to selinexor, Karyopharm's pipeline includes second-generation SINE compounds and combination studies in solid tumors and hematologic malignancies.

Founded in 2008 and headquartered in Newton, Massachusetts, Karyopharm has built a research platform around modulation of nuclear export pathways.

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