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Abstracts

Characterization of Long-Term Seizure Freedom in the Ongoing Open-Label Extension of X-TOLE: Potential Implications for Future Clinical Practice

Abstract number : 1.377
Submission category : 7. Anti-seizure Medications / 7B. Clinical Trials
Year : 2025
Submission ID : 926
Source : www.aesnet.org
Presentation date : 12/6/2025 12:00:00 AM
Published date :

Authors :
Presenting Author: Danielle Becker, MD, MS – The Ohio State University Wexner Medical Center

Jacqueline French, MD – Department of Neurology and Comprehensive Epilepsy Center, New York University Grossman School of Medicine, NYU Langone Health
Jenny Qian, MS – Xenon Pharmaceuticals Inc.
Lee Gervitz, PhD – Xenon Pharmaceuticals Inc.

Rationale: Although seizure freedom remains the ultimate goal in epilepsy management, real-world clinical practice reveals that most patients face a fluctuating journey of achieving, losing, and regaining periods of seizure control. The variability in individual patient experiences suggests that a single, standardized duration of seizure freedom may be insufficient to help inform realistic treatment expectations and guide clinical management. Open-label extension (OLE) studies can allow ongoing observation of seizure patterns, enabling the calculation of various seizure-free intervals to better characterize dynamic patterns of treatment response. Using long-term data from the ongoing 7-year X-TOLE OLE study (French 2025) of azetukalner, a Kv7 potassium channel opener, in focal onset seizures (FOS), we report multiple seizure freedom analyses to better understand how periods of complete seizure control are achieved and maintained.

Methods: Participants completing the X-TOLE double-blind period (DBP) started the OLE on azetukalner 20 mg once daily with food. Seizure freedom, defined as a complete 100% reduction in seizures from OLE baseline, was assessed post hoc over consecutive durations at any specified interval during the study or since the last study visit. In those who completed ≥42 months in the OLE, the proportion of participants who had achieved ≥12 months of seizure freedom as of their last study visit, as well as the subset who also had seizure freedom for ≥24 and ≥36 months, were assessed. Among those participants who initially achieved 1 interval of seizure freedom for any ≥6 consecutive months but subsequently had a seizure, attainment of subsequent seizure-free intervals of ≥6 or ≥12 consecutive months was assessed.

Results: Of the 285 X-TOLE DBP completers, 275 (96.5%) enrolled in the OLE. Median DBP baseline FOS frequency was 13.5/month. Of all OLE participants, 137 (49.8%) were treated for ≥42 months as of April 1, 2025. Among them, 26.3% (36/137) had achieved ≥12 months of seizure freedom; of these participants 77.8% (28/36) had ≥24 months and 58.3% (21/36) had ≥36 months seizure freedom from last study visit. 46.7% (64/137) achieved one interval of seizure freedom for any ≥6 consecutive months. Of those participants, 48.4% (31/64) had a subsequent seizure, 71.0% (22/31) regained ≥6 months, and 58.1% (18/31) regained ≥12 months of subsequent seizure freedom. The mean duration of the regained consecutive period of seizure freedom in these 31 participants was 17.5 months (median, 13 months). Safety and additional seizure freedom data will be presented.

Conclusions: This post hoc analysis of the X-TOLE OLE highlights the potential of azetukalner to support long-term seizure freedom. These findings may help inform future clinical decision making by providing a more nuanced understanding of treatment response patterns over time, including the possibility to regain periods of seizure freedom with long-term treatment with azetukalner.

Funding: Xenon Pharmaceuticals Inc.

Anti-seizure Medications