New phase 3 trial results presented at the 2026 American Academy of Neurology Annual Meeting suggest that the investigational anti-seizure medication Azetukalner may offer substantial seizure reduction for adults with treatment-resistant focal onset seizures.
The data were presented by Xenon Pharmaceuticals from the phase 3 X-TOLE2 study, which evaluated azetukalner as an add-on therapy in adults with focal epilepsy. The randomised, double-blind trial included 380 participants with highly treatment-resistant disease, many of whom had previously failed multiple anti-seizure medications.
Patients receiving the 25 mg dose experienced a 53.2% median reduction in monthly seizure frequency during the 12-week double-blind treatment period, compared with a 10.4% reduction in the placebo group. The lower 15 mg dose was associated with a 34.5% reduction. Researchers also reported improvements in responder rates across several thresholds, including reductions of at least 50%, 75% and 90% in seizure frequency.
Notably, complete seizure freedom increased over time during treatment. By the final four weeks of the double-blind period, 13.7% of patients receiving the 25 mg dose achieved a 100% reduction in seizures, compared with 4% of those receiving placebo.
| Sign up to the ACNR email newsletter here |
Long-term findings from the ongoing X-TOLE open-label extension study were also presented. Among participants treated with azetukalner for at least 48 months, nearly 40% achieved seizure freedom for at least 12 consecutive months, while approximately one-quarter remained seizure-free for at least 24 months.
The company said the treatment continued to demonstrate a generally favourable safety and tolerability profile over extended follow-up. The most commonly reported adverse events included dizziness, headache, somnolence and fatigue. No major cardiovascular safety concerns or significant weight gain were reported during the double-blind phase.
Researchers also highlighted potential practical advantages of azetukalner, including once-daily dosing and no requirement for dose titration. Real-world data presented at the meeting suggested both clinicians and patients viewed titration-free treatment approaches as potentially less stressful and easier to manage.
Xenon Pharmaceuticals said it plans to submit a New Drug Application to the US Food and Drug Administration during the third quarter of 2026.
This news item has been summarised using AI and checked by humans before publication.
Sources
American Academy of Neurology Annual Meeting
| Sign up for our online community for neurology specialists |
