Azetukalner, a Novel, Potent KV7 Channel Opener, in Adults with Focal Epilepsy: ≥42-Month Interim Analysis of the Ongoing 7-year X-TOLE Open-label Extension
Jacqueline French1, Roger Porter2, Emilio Perucca3, Martin Brodie4, Cynthia Harden5, Jenny Qian5, Constanza Luzon Rosenblut5, Christopher Kenney5, Gregory Beatch5
1New York University Grossman School of Medicine and NYU Langone Health, 2University of Pennsylvania, 3Department of Medicine (Austin Health), The University of Melbourne and Department of Neuroscience, Monash University, 4University of Glasgow Department of Medicine and Therapeutics, Western Infirmary, 5Xenon Pharmaceuticals Inc.
Objective:
To provide the latest X-TOLE interim open-label extension (OLE) results
Background:
Azetukalner, a novel, potent KV7 channel opener, is in development for focal onset seizures (FOS), primary generalized tonic-clonic seizures, major depressive disorder, and bipolar depression. The efficacy and safety of azetukalner in FOS have been reported from the randomized, placebo-controlled phase 2b X-TOLE trial and the ongoing 7-year OLE. We report the latest interim OLE results (April 1, 2025).
Design/Methods:
Eligible participants from the double-blind period (DBP) started the OLE on azetukalner 20 mg once daily with food. Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and were assessed.
Results:
In total, 275 participants (96.5%) enrolled in the OLE from the DBP. Baseline median monthly FOS frequency was 13.5; 52.4% were taking 3 concomitant antiseizure medications. As of April 1, 2025, 182, 165, and 135 participants received treatment for ≥12, ≥24, and ≥42 months, respectively; 123 (44.7%) are ongoing. The most common reasons for discontinuation were lack of efficacy (18.2%) and study withdrawal (16.7%). The most common TEAEs were dizziness (23.3%), headache (18.2%), COVID-19 (17.1%), somnolence (16.4%), fall (14.2%), weight increased (11.3%), and memory impairment (10.5%). In total, 15.6% of participants reported ≥1 SAE; 2.5% were considered treatment related. During the DBP and OLE, 2 deaths were reported (sudden unexpected death in epilepsy and viral pneumonia, n=1 each), neither considered treatment related. The MPC in seizure frequency was −87% in participants continuing at 42 months in the OLE. Updated safety and efficacy data will be presented.
Conclusions:
In the ongoing X-TOLE OLE, azetukalner was generally well tolerated, with no new safety signals. These data support the long-term safety and efficacy of azetukalner in a difficult-to-treat population of patients with FOS.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.