Xenon pauses Phase 3 depression trials of azetukalner after side-effect reports

What's the news? Xenon Pharmaceuticals has paused new enrolment in two Phase 3 depression trials — X-Nova2 in major depressive disorder and X-Ceed in bipolar depression — after some participants reported neuropsychiatric side effects, including a small number of cases described as psychosis. The company said the pause was a precautionary step taken with its safety monitoring board; patients already enrolled continue treatment.

Why it matters: The trials test azetukalner, a small molecule that activates potassium channels in the brain — a mechanism Xenon hopes can treat depression differently from existing antidepressants. X-Nova2 had already enrolled about 360 participants, roughly 80% of its target, so the pause is a significant setback for the programme. Xenon said it is evaluating possible dose modifications to improve tolerability. Notably, the company separately submitted azetukalner for FDA review in focal seizures (epilepsy), where it remains in development.

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