azetukalner (XEN1101) - (X-NOVA)

September 17, 2026: Xenon Pharmaceuticals (NASDAQ: XENE) submitted an NDA to the FDA for azetukalner for focal seizures. The filing is based on positive Phase 2b X-TOLE and Phase 3 X-TOLE2 randomized, placebo-controlled trials, in which all four azetukalner doses showed statistically significant reductions from baseline in monthly seizure frequency versus placebo; the drug was generally well tolerated, with safety described as consistent across studies and supported by more than 1,500 patient-years of epilepsy exposure data.

Azetukalner’s epilepsy expansion studies remain ongoing: Phase 3 X-TOLE3 in focal onset seizures and Phase 3 X-ACKT in primary generalized tonic-clonic seizures are still enrolling.

In psychiatry, Xenon said it has voluntarily paused enrollment of new patients in ongoing major depressive disorder and bipolar depression studies after analyzing neuropsychiatric adverse events. Current participants in randomized and open-label extension studies will remain on study. The company said the events were consistent with azetukalner’s known safety/tolerability profile and is evaluating dosing modifications. The pause does not affect epilepsy studies.

For MDD, X-NOVA2 enrollment is complete at about 360 patients, roughly 80% of the original 450-patient target, and Xenon said the trial remains sufficiently powered for the primary HAM-D17 endpoint. Topline X-NOVA2 data are now expected in Q1 2027.