Xenon Files Azetukalner NDA as It Pauses Psychiatry Trials for Tolerability Review

Xenon Files Azetukalner NDA as It Pauses Psychiatry Trials for Tolerability Review

Xenon filed an NDA for azetukalner to treat focal-onset seizures, supported by positive X-TOLE and X-TOLE2 results and more than 1,500 patient-years of epilepsy exposure. FDA review is expected to take about 12 months, with potential DEA scheduling adding roughly three months after approval. Psychiatry trials have been paused while Xenon evaluates dose-escalation changes intended to improve tolerability in major depressive disorder and bipolar depression studies. The company said the adverse events under review, including dizziness, somnolence and occasional cognitive effects, are known and generally not serious, and that the epilepsy program is unaffected. Xenon expects its pain candidates XEN1701 and XEN1120 to enter Phase 2 proof-of-concept studies in 2027, while a separate Nav1.7 program has begun Phase 1 testing.

Xenon Pharmaceuticals NASDAQ: XENE said it has filed its first new drug application for azetukalner as a treatment for focal-onset seizures, while pausing portions of its late-stage psychiatry program to evaluate changes intended to improve tolerability. Speaking at the 2026 TD Cowen Neuropsychiatry Summit, President and CEO Ian Mortimer said the NDA submission for azetukalner in focal-onset seizures is supported by the company’s X-TOLE and X-TOLE2 randomized, placebo-controlled studies. Mortimer said X-TOLE2, for which results were released in March, showed what Xenon believes was the strongest placebo-adjusted efficacy demonstrated in a focal-onset seizure study.

The company has also accumulated 1,500 patient-years of epilepsy exposure for azetukalner, including patients from the X-TOLE trial who have received the medicine for more than five years, Mortimer said. Xenon plans to present updated 60-month open-label X-TOLE data at the American Epilepsy Society meeting in December. The company said the long-term data have shown seizure reductions and longer periods of seizure freedom.

Xenon expects a standard FDA review rather than priority review for the epilepsy application. The company is modeling a 12-month review from its September 2026 filing, although it intends to advocate for the drug during the review process. Kelly added that Drug Enforcement Administration scheduling, which is common for anti-seizure medicines, could add approximately three months after NDA approval.

Mortimer said the company filed for four azetukalner doses: 10 milligrams, 15 milligrams, 20 milligrams and 25 milligrams. While all four doses demonstrated statistical separation from placebo in seizure reduction, he said Xenon expects physicians may commonly begin patients at 15 milligrams, reflecting the general practice of starting anti-seizure medicines at lower doses. According to Mortimer, the 10-milligram and 15-milligram doses were nearly indistinguishable from placebo in safety tables, aside from somewhat more dizziness at 15 milligrams. He said azetukalner’s once-daily administration, lack of required titration and limited drug-drug interaction concerns could make it easier to use for both epilepsy specialists and general neurologists.

Xenon has hired Darren Cline as chief commercial officer and has built a commercial leadership team ahead of a potential launch. Kelly said the company views azetukalner as having potential to reach a broader group of prescribers than XCOPRI, but he did not provide launch guidance. He said anti-seizure medicine launches historically can be gradual and that Xenon expects to provide additional qualitative guidance closer to a pot...