Drug pipeline
Novel agent cuts seizures, shows durable control in late-breaking AAN data
Clinical Takeaway: Azetukalner may offer a no-titration option with rapid onset and sustained seizure control, including meaningful long-term seizure freedom, for adults with focal onset seizures.
In a population with a median of 13 seizures per month and heavy prior therapy, a single daily dose produced one of the largest placebo-adjusted seizure reductions reported in a pivotal focal epilepsy trial.
Xenon Pharmaceuticals reported positive phase 3 and long-term results for azetukalner, a novel KV7 potassium channel opener, at the 2026 American Academy of Neurology meeting. In the randomized, double-blind X-TOLE2 study, patients receiving azetukalner 25 mg achieved a 53.2% median reduction in monthly focal seizures over 12 weeks, compared with a 10.4% reduction on placebo. The placebo-adjusted effect (–42.7%) was described by the company as the strongest seen to date in a pivotal focal onset seizure study.
Notably, nearly 60% of enrolled patients were taking or had discontinued cenobamate, underscoring the refractory nature of the population. Rates of complete (100%) seizure reduction increased over the double-blind treatment period, suggesting benefit with continued exposure.
New 48-month data from the ongoing open-label extension showed durable outcomes: nearly 40% of participants achieved at least 12 consecutive months of seizure freedom, and about 25% reached 24 months or more.
“Our data highlight the potential of azetukalner to become a preferred medication for addressing uncontrolled seizures,” said Chris Kenney, MD, Xenon’s chief medical officer. “Equally remarkable was the ability for some patients to gain complete seizure control the longer they remained on therapy.”