Xenon Presents Positive Azetukalner Phase 3 Data at AAN Annual Meeting

Azetukalner demonstrates best-in-class efficacy and long-term seizure freedom in focal onset seizures

Apr. 19, 2026 at 10:30pm

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An extreme close-up X-ray image revealing the intricate internal structure of a human brain neuron, with glowing, ghostly lines against a dark background, conceptually illustrating the novel mechanism of action of the anti-seizure medication azetukalner.Azetukalner's unique mechanism of action as a potent potassium channel opener could provide a new approach to addressing the unmet needs of epilepsy patients struggling with uncontrolled focal seizures.Boston Today

Xenon Pharmaceuticals presented positive data from the Phase 3 X-TOLE2 study and long-term X-TOLE open-label extension, highlighting the efficacy and safety of its novel anti-seizure medication azetukalner in treating focal onset seizures. The data showed significant reductions in seizure frequency and increasing rates of complete seizure control over time, with nearly 40% of patients achieving at least 12 months of seizure freedom after 48 months of treatment.

Why it matters

The robust clinical data for azetukalner underscores its potential to become a preferred medication for addressing uncontrolled focal onset seizures, which affect up to half of epilepsy patients despite the availability of numerous treatment options. Azetukalner's unique mechanism of action as a potent K V 7 potassium channel opener, combined with its ease-of-use benefits like no titration and once-daily dosing, could provide much-needed innovation in the anti-seizure medication landscape.

The details

The Phase 3 X-TOLE2 study showed that treatment with 25 mg or 15 mg azetukalner resulted in statistically significant 53.2% and 34.5% reductions, respectively, in monthly focal onset seizure frequency compared to 10.4% for placebo. Dose-dependent increases were also seen in the proportion of patients achieving 50%, 75%, and 90% reductions in seizures. Importantly, the data demonstrated increasing rates of complete 100% seizure reduction over time, with 10.5% of patients in the 25 mg group achieving this milestone in the last 8 weeks of the 12-week double-blind period. The long-term X-TOLE open-label extension data further reinforced azetukalner's efficacy, with nearly 40% of patients treated for at least 48 months achieving at least 12 months of seizure freedom.

  • The X-TOLE2 study was a 12-week double-blind, placebo-controlled Phase 3 trial.
  • The X-TOLE open-label extension study is ongoing for 7 years, with data presented from the ≥48-month interim analysis.

The players

Xenon Pharmaceuticals Inc.

A neuroscience-focused biopharmaceutical company developing azetukalner, a novel anti-seizure medication, for the treatment of epilepsy, major depressive disorder, and bipolar depression.

Chris Kenney, MD

Chief Medical Officer of Xenon Pharmaceuticals.

Ian Mortimer

President and CEO of Xenon Pharmaceuticals.

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What they’re saying

“Our data at the 2026 AAN meeting highlight the potential of azetukalner to become a preferred medication for addressing uncontrolled seizures.”

— Chris Kenney, MD, Chief Medical Officer of Xenon Pharmaceuticals

“Across the X-TOLE, X-TOLE OLE, and X-TOLE2 studies, we have observed robust efficacy as early as week 1, increasing seizure control through the double-blind and open-label periods, impressive seizure freedom over time, including the ability to regain extended periods of seizure freedom with azetukalner in the event of a breakthrough seizure, and a consistent and generally well-tolerated safety profile.”

— Ian Mortimer, President and CEO of Xenon Pharmaceuticals

What’s next

Xenon is working to submit a New Drug Application to the FDA for azetukalner in the third quarter of 2026, bringing the medication one step closer to reaching clinicians and patients.

The takeaway

The positive clinical data for azetukalner, including its ability to provide robust seizure control and high rates of long-term seizure freedom, position it as a potentially transformative new option for the large population of epilepsy patients with uncontrolled focal onset seizures who continue to struggle with the burden of their condition.