Karyopharm Therapeutics has suffered a severe blow after its flagship drug selinexor, sold as Xpovio, failed to meet its primary endpoint in a Phase 3 endometrial cancer trial.
The XPORT-EC-042 trial evaluated selinexor as a maintenance therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer, and the results disappointed across the board.
In the modified intent-to-treat population of 236 patients, median progression-free survival was 12.75 months with selinexor compared to 7.43 months with placebo.
The hazard ratio came in at 0.76, with a one-sided p-value of 0.0791, falling short of the threshold required to declare statistical significance on the primary endpoint.
Shares in Karyopharm (KPTI) cratered by approximately 65% following the announcement, reflecting the severity of the setback for the company’s growth ambitions.
This marked the second failed attempt by Karyopharm to expand Xpovio, a drug originally developed for blood cancers, into the endometrial cancer market.
Despite the failure, safety data from the trial remained consistent with the drug’s established profile, and no new safety signals were identified during the study period.
CEO Richard Paulson moved quickly to reassure investors, stating: “While the results we are announcing today fell short of our expectations, they do not diminish our confidence in the broader potential of selinexor and benefit of XPO1 inhibition.”
Paulson added: “We remain focused on maximizing our opportunity in myelofibrosis and continuing to build on our profitable multiple myeloma business.”
Karyopharm now intends to reduce planned investment in endometrial cancer and redirect resources toward its myelofibrosis programme, where the company sees its most significant near-term opportunity.
The company plans to submit a supplemental New Drug Application to the FDA in August 2026, seeking accelerated approval for selinexor combined with ruxolitinib in myelofibrosis patients.
That application will be supported by Phase 3 SENTRY trial data showing statistically significant SVR35 spleen responses at week 24, along with supportive survival, biomarker findings, and an acceptable overall safety profile.
Karyopharm also expects topline data from the 60 mg cohort of the Phase 2 SENTRY-2 trial to arrive in the second half of 2026, adding another potential catalyst for the myelofibrosis programme.
The company anticipates that selinexor could be added to relevant compendia guidelines for myelofibrosis, a step that would significantly support commercial uptake of the drug in that indication.
Karyopharm’s multiple myeloma franchise continues to generate revenue and remains a stable foundation as the company absorbs the financial and reputational impact of the endometrial cancer failure.