Xenon Pharmaceuticals reported positive Phase 3 data for azetukalner, a novel KV7 channel opener being developed for focal onset seizures, presented at the American Academy of Neurology Annual Meeting in April. The X-TOLE2 trial showed that azetukalner 25 mg achieved a 53.2% reduction in monthly seizure frequency compared to 10.4% for placebo over a 12-week double-blind period. Among participants with treatment-resistant epilepsy, 6.5% of those receiving 25 mg achieved complete seizure freedom versus 0.8% in the placebo group.
Long-term data from the ongoing X-TOLE open-label extension study demonstrated sustained efficacy over 48 months. Among participants treated for at least 48 months, nearly 40% achieved at least 12 months of seizure freedom, and one in four achieved at least 24 months of seizure freedom. Monthly seizure frequency reductions increased from 69.8% at month one in the extension to 90.9% at month 48.
The safety profile remained consistent across studies. The most common adverse events were dizziness (20.5%), headache (8.8%), somnolence (8.8%), and fatigue (7.6%) in the 25 mg group. No serious adverse events occurred at elevated rates, and no cases of weight gain, severe allergic rashes, retinal abnormalities, or notable cardiovascular events were reported.
The trial enrolled 380 participants with highly treatment-resistant epilepsy, with a median baseline seizure frequency of 12.75 per month and a median of five prior anti-seizure medications. Approximately 60% had previously taken or discontinued cenobamate. Xenon plans to submit a New Drug Application to the FDA in the third quarter of 2026. The company also emphasized the value of azetukalner’s no-titration design, noting that patient feedback indicated 90% felt this would boost confidence, 77% reported it would reduce anxiety, and 84% believed it would improve medication adherence.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.benzinga.com/pressreleases/26/04/g51904056/xenon-presents-azetukalner-phase-3-x-tole2-study-results-and-48-month-long-term-data-in-focal-onse