Long-Term Safety and Efficacy of Azetukalner (XEN1101), a Novel, Potent KV7 Potassium Channel Opener in Adults With Focal Epilepsy: Update From the Ongoing 7-Year Open-Label Extension of X-TOLE
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, 3Monash University and University of Melbourne (Austin Health), 4University of Glasgow Department of Medicine and Therapeutics, Western Infirmary, 5Xenon Pharmaceuticals Inc.
Objective:
This abstract reports 30-month data from the X-TOLE 7-year open label extension (OLE) study of azetukalner in participants with focal onset seizures (FOS).
Background:
In the double-blind period (DBP) of X-TOLE, azetukalner (10, 20, and 25 mg once daily [QD] with food with no titration period) showed dose-dependent, statistically significant, and rapid-onset reductions in FOS frequency.
Design/Methods:
Eligible participants in the OLE received 20 mg QD with food. Assessments were performed at week 3 in the OLE and at 3-month intervals thereafter. Safety assessments included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and significant changes in laboratory findings. Primary efficacy outcome was median percentage change (MPC) in monthly (28-day) FOS frequency from DBP baseline.
Results:
285 participants completed the DBP, and 275 (96.5%) enrolled in the OLE. At this interim analysis of the OLE (data cut April 2024), 182 participants had been treated for ≥12 months and 152 for ≥30 months. 142 (51.6%) are ongoing. TEAEs were reported in 241 (87.6%) participants, and were treatment related in 172 (62.5%). The majority were mild or moderate; 46 participants (16.7%) reported severe TEAEs. The most common TEAEs were dizziness (22.5%), coronavirus infection (16.4%), headache (16.0%), somnolence (13.8%), fall (13.1%), memory impairment (11.6%), and weight increase (10.5%). Mean (SD) weight gain was 0.32 (8.0) kg at 2.5 years in the OLE. SAEs were reported in 39 (14.2%); and considered treatment related in 6 (2.2%). There were 2 cases of sudden unexpected death in epilepsy reported as non treatment related. The MPC was –86.9% at 30 months in the OLE. Updated safety and efficacy analyses will be presented.
Conclusions:
In the ongoing X-TOLE OLE, azetukalner was generally well tolerated with no new safety signals. These promising interim data continue to suggest long-term safety and efficacy of azetukalner in a difficult-to-treat population.
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