Potassium Channel Opener Promising for Seizure Freedom

Of the 285 participants who completed the X-TOLE double-blind period (DBP), 275 (96.5%) enrolled in the OLE and started the OLE on azetukalner 20 mg once daily. The median DBP baseline was 13.5 FOS per month, and seizure freedom was defined as a 100% reduction in FOS. In participants treated for at least 48 months (131), investigators assessed the proportions achieving seizure freedom for at least 12, 24, 36, and 48 months as well as patterns of regaining seizure-free intervals after breakthrough events.

Key findings from poster presentations at AES 2025 included:

• 38.2% (50/131) achieved at least 12 months of seizure freedom.
• 25.2% (33/131) of that group maintained seizure freedom for at least 24 months, 19.8% (26/131) maintained seizure freedom for at least 36 consecutive months, and 10.7% (14/131) maintained seizure freedom for at least 48 consecutive months.
• Participants treated for at least 48 months experienced a median percent reduction in monthly seizure frequency of 90.9% from baseline.
• Among patients who initially achieved 6 months of seizure freedom but subsequently experienced a seizure, 69.7% (23/33) regained at least 6 months of subsequent seizure freedom, and 57.6% (19/33) regained at least 12 months of subsequent seizure freedom.
• The mean duration of regained seizure-free periods was 18.9 months​.

Sources: Becker D, French J, Qian J, et al. Characterization of long-term seizure freedom in the ongoing open-label extension of X-TOLE: potential implications for future clinical practice. Presented at: American Epilepsy Society Annual Meeting; December 5–9, 2025; Atlanta, GA. Poster 1.377

French JA, Porter RJ, Perucca E, et al. Long-term safety and efficacy of azetukalner, a novel, potent Kv7 potassium channel opener, in adults with focal epilepsy: ≥48-month interim analysis of the ongoing 7-year X-TOLE open-label extension. Presented at: American Epilepsy Society Annual Meeting; December 5–9, 2025; Atlanta, GA. Poster 3.356.