Xenon's azetukalner shows unprecedented efficacy in focal seizure trial

Xenon Pharmaceuticals has released its first-quarter financial results for 2026 alongside updates on its drug development programmes. The company’s lead candidate, azetukalner, showed strong results in a recent trial for focal onset seizures (FOS). Plans are now underway to submit the treatment for regulatory approval in the US by late 2026.

The Phase 3 X-TOLE2 study of azetukalner in FOS met its primary goal. Patients on the 25 mg dose saw a 53.2% median reduction in monthly seizure frequency, while the 15 mg group experienced a 34.5% decrease. The placebo group recorded just a 10.4% drop. According to Xenon, the 25 mg dose achieved the highest placebo-adjusted efficacy ever seen in a pivotal FOS trial.

Enrolment is still open for additional Phase 3 studies of azetukalner. The X-TOLE3 trial focuses on FOS for non-US regulatory submissions, while the X-ACKT study targets primary generalised tonic-clonic seizures (PGTCS). Meanwhile, recruitment continues for Phase 3 trials in major depressive disorder (X-NOVA2 and X-NOVA3) and bipolar depression (X-CEED). Beyond azetukalner, Xenon is advancing other programmes. A Phase 1b study of NBI-921355, developed with Neurocrine Biosciences for epilepsy, is ongoing, with data due in 2027. Phase 1 trials for XEN1701 (targeting NaV1.7) and XEN1120 (targeting KV7) in pain are set to finish in the second half of 2026. Pre-clinical research on Xenon’s NaV1.1 programme for Dravet syndrome also showed promising results, improving motor function, seizure control, and cognitive performance in test models.

Xenon expects to file a New Drug Application (NDA) for azetukalner in FOS with the US FDA in the third quarter of 2026. The company’s pipeline includes ongoing trials for epilepsy, depression, and pain treatments, with key data readouts planned over the next two years. Financial results for the first quarter of 2026 were also reported as part of the update.