Xenon Pharmaceuticals Submits New Drug Application to FDA for Azetukalner for the Treatment of People with Focal Seizures

Xenon Pharmaceuticals submitted a New Drug Application (NDA) to the Food and Drug Administration (FDA) for azetukalner (Xenon Pharmaceuticals, Needham, MA) for the treatment of people with focal seizures, according to an announcement from the company. Azetukalner is an investigational oral KV7 potassium channel opener under evaluation for epilepsy and psychiatric indications. The agent is designed to modulate potassium channels in the central nervous system, which may reduce excessive neuronal firing.

The NDA is supported by data from 2 global, randomized, double-blind, placebo-controlled trials in focal seizures: the phase 2b X-TOLE (NCT03796962) and phase 3 X-TOLE2 (NCT05614063) clinical trials. According to a statement from Xenon Pharmaceuticals, participants treated with azetukalner across 4 evaluated doses showed statistically significant reductions from baseline in monthly seizure frequency compared with those receiving placebo. The company also reported that azetukalner was generally well tolerated, with a consistent safety profile across the 2 studies and long-term safety data from the X-TOLE open-label extension. The epilepsy program has generated more than 1500 patient-years of safety and exposure data.

Clinical Program Updates

• X-TOLE3, an ongoing phase 3 study in focal onset seizures, continues to enroll participants.
• X-ACKT, an ongoing phase 3 study in primary generalized tonic-clonic seizures, also remains active.
• Xenon Pharmaceuticals voluntarily paused enrollment of new participants in ongoing major depressive disorder and bipolar depression studies after reviewing neuropsychiatric adverse events in those programs.
• Participants already enrolled in the psychiatry randomized controlled studies and open-label extension studies will continue in the trials.
• Xenon Pharmaceuticals stated that the psychiatry enrollment pause does not affect ongoing epilepsy studies.

Practical Implications in the Clinic

For epilepsy clinicians, the NDA submission represents a regulatory milestone for an investigational antiseizure therapy with a potassium channel–modulating mechanism. Full assessment will depend on FDA review and detailed publication or presentation of the pivotal focal seizure data, including efficacy by dose, adverse events, discontinuations, and concomitant antiseizure medication use.

Source

Xenon Pharmaceuticals. Xenon announces azetukalner NDA submission to FDA for focal seizures and provides update on psychiatry clinical program. Published September 17, 2026. Accessed September 24, 2026. https://investor.xenon-pharma.com/news-releases/news-release-details/xenon-announces-azetukalner-nda-submission-fda-focal-seizures