Shares of Xenon Pharmaceuticals Inc. (NASDAQ:XENE) surged 40% on Monday after the company reported positive topline data from its Phase 3 X-TOLE2 trial evaluating azetukalner for focal onset seizures.
The study achieved its primary endpoint in both tested dose groups. Patients receiving the 25 mg dose experienced a median reduction of 53.2% in monthly focal onset seizure frequency from baseline, compared with a 10.4% reduction in the placebo group. The placebo-adjusted median reduction of 42.7% for the 25 mg dose exceeded the results seen in the company’s earlier Phase 2b X-TOLE trial, which recorded a placebo-adjusted reduction of 34.6% for the same dose.
The trial also met its key secondary endpoint, Responder Rate 50. In the study, 54.8% of patients in the 25 mg group and 37.6% in the 15 mg group achieved at least a 50% decrease in monthly seizure frequency, compared with 20.8% of participants receiving placebo.
A total of 380 patients with highly treatment-resistant epilepsy were enrolled in the trial. Participants had previously tried a median of five antiseizure medications and reported a baseline average of 12.75 seizures per month. Of the 332 participants who completed the double-blind portion of the study, 322 chose to continue into the open-label extension phase.
Azetukalner was generally well tolerated, with a safety profile consistent with results from the earlier X-TOLE trial. The most commonly reported treatment-emergent adverse events across both dose groups included dizziness, headache, somnolence and fatigue.
Xenon said it plans to submit a New Drug Application to the U.S. Food and Drug Administration in the third quarter of 2026 seeking approval of azetukalner for the treatment of focal onset seizures. If approved, the therapy would become the only KV7 potassium channel opener available for epilepsy treatment.
Stifel analysts commented, “we think the results here could lead investors to reconsider their peak penetration and peak sales assumptions.”