Abstract Details

Report initial findings from the randomized, double-blind, placebo-controlled, Phase 3 study X-TOLE2 (NCT05614063) evaluating azetukalner (AZK) for FOS.

The K_V7 channel opener AZK showed significant, dose-dependent reductions in FOS frequency in X-TOLE (Phase 2b). The X-TOLE2 study has been completed. Results from these pivotal studies will support the planned New Drug Application for AZK in FOS.

Following an 8-9.5–week baseline period, eligible adults (aged ≥18 years) taking 1-3 antiseizure medications (ASMs) were randomized 1:1:1 to receive AZK (25 or 15 mg) or placebo with food once daily for 12 weeks with no titration period. Randomization was stratified by baseline CYP3A4 inducer use. The primary endpoint was median percentage change (MPC) in monthly FOS frequency (baseline through double-blind period [DBP], AZK versus placebo). Key secondary endpoints (AZK versus placebo) included proportion of participants experiencing ≥50% reduction in monthly FOS frequency (baseline through DBP), MPC in weekly FOS frequency (baseline to Week 1), and proportion scoring “much improved” or better on the Patient Global Impression of Change at Week 12. Safety endpoints included severity and frequency of treatment-emergent and serious adverse events. Eligible participants were offered the option of entering an open-label extension study.

380 participants were randomized. At baseline, the mean (SD) age was 39.9 (12.9) years (disease onset at 15.9 [13.2] years), 51.1% were female, and 42.1% were from North America. Participants had tried and discontinued a median of 5 (IQR 3.0-9.0) ASMs before study entry; 256 (67.4%) were taking CYP3A4 inducer(s); 39 (10.3%), 143 (37.6%), and 193 (50.8%) were taking 1, 2, and 3 background ASMs, respectively. Baseline median monthly FOS frequency was 12.7 (IQR 7.6-33.3). Efficacy and safety results will be presented.

X-TOLE2 results will support the regulatory submission of AZK in FOS and could mark the next generation of ASMs available to people living with epilepsy.