Safety signals prompt Xenon to pause enrollment in azetukalner psychiatry trials

Xenon Pharmaceuticals has voluntarily paused new-patient enrollment in its azetukalner trials for major depressive disorder (X-NOVA2) and bipolar depression (X-CEED) after reviewing neuropsychiatric adverse events. Existing participants and associated open-label-extension studies can continue.

Reported events included confusion, speech/language difficulty (aphasia), impaired coordination/ataxia, and a very small number categorized as psychosis. Xenon’s chief medical officer said psychosis was around 1% or less, and the company characterized events as generally short-lived and reversible without known long-term effects.

Xenon says the frequency and severity are consistent with azetukalner’s known mechanism and prior safety experience, but noted that these events had not appeared in its earlier Phase 2 X-NOVA MDD study. The pause was made with the Data Safety Monitoring Board and is intended to be temporary.

The company is evaluating dose modifications to improve tolerability. The pause does not affect azetukalner’s epilepsy program, for which Xenon submitted an FDA new-drug application for focal seizures at the same time.

The disclosure unsettled investors:
reports indicated Xenon shares fell sharply in after-hours trading and subsequently, reflecting added uncertainty over the psychiatric indications and their development timeline.