Xenon Pharmaceuticals Inc. reports Phase 3 data showing azetukalner significantly reduces focal onset seizures, with sustained efficacy and favourable safety, ahead of planned U.S. Food and Drug Administration submission in Q3 2026.
Written By: Karthik Teja Macharla, PharmD
Reviewed By: Pharmacally Editorial Team
Xenon Pharmaceuticals Inc. presented Phase 3 results for azetukalner in adults with focal onset seizures (FOS) at the American Academy of Neurology Annual Meeting 2026 in Chicago, including data from the X-TOLE2 trial, long-term extension analyses, and real-world evidence supporting its once-daily, no-titration use.
In the 12-week X-TOLE2 double-blind study (NCT05614063), azetukalner demonstrated statistically significant reductions in seizure frequency in a treatment-resistant population. Median monthly seizure reductions were 53.2% with the 25 mg dose and 34.5% with the 15 mg dose, compared with 10.4% for placebo, with effects observed from week one and sustained throughout the study period. Dose-dependent improvements were seen across ≥50%, ≥75%, and ≥90% responder rates, and a higher proportion of patients achieved seizure freedom compared with placebo, with rates increasing over time.
The safety profile was consistent with prior studies, with dizziness, headache, somnolence, and fatigue reported as the most common adverse events. Serious adverse events were infrequent and similar across treatment groups, with no notable signals related to weight gain, cardiovascular events, or retinal abnormalities.
Long-term findings from the ongoing X-TOLE open-label extension, representing more than 775 patient-years of exposure, showed sustained efficacy, with median seizure reductions improving from 69.8% at month one to 90.9% at month 48. Among patients treated for 48 months, 38.2% achieved at least 12 months of seizure freedom.
Real-world data highlighted the burden of anti-seizure medication titration for both patients and clinicians, with findings indicating that no-titration approaches may improve treatment adherence and reduce complexity in care.
Chris Kenney, Chief Medical Officer of Xenon Pharmaceuticals Inc., stated that azetukalner demonstrated strong efficacy in patients with high seizure burden and prior treatment exposure, including evidence of sustained seizure control over time.
Ian Mortimer, President and Chief Executive Officer, highlighted the therapy’s early onset of action, consistent long-term efficacy, favourable tolerability profile, and simplified dosing, and noted that the company plans to submit a New Drug Application to the U.S. Food and Drug Administration in the third quarter of 2026.
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About the Writer
Karthik Teja Macharla, PharmD is a Pharm.D. graduate with a strong interest in clinical research, pharmacovigilance, and medical writing. In his words, he is passionate about converting complex medical information into clear, evidence-based scientific communication, committed to contributing to patient safety and advancing healthcare through accurate and impactful medical content.