Wide range of cenobamate doses associated with initial seizure freedom in patients with uncontrolled focal seizures: Post-hoc analysis of a phase 3, multicenter, open-label study

OBJECTIVE: To examine initial doses of cenobamate that were associated with seizure freedom (100% seizure reduction) in a subset of patients from a large, open-label, phase 3 safety study. METHODS: We reviewed available focal seizure efficacy data for patients (N = 240) from 10 eligible US study sites. Among patients achieving seizure freedom for ≥12 months (≥350 consecutive days) and ≥24 months (≥700 consecutive days) at last clinic visit, or at any time during the analysis, the doses of cenobamate at the start of their seizure-free interval were examined. We also examined cenobamate doses for ≥12-month and ≥24-month seizure freedom stratified by baseline seizure frequency (< 3 vs ≥3 seizures/28 days). RESULTS: Of 62 patients with ≥12-month seizure freedom at their last visit, 24.2 % (15/62) of patients started their seizure-free interval at cenobamate doses ≤50 mg/day, 4.8 % (3/62) at 100 mg/day, 14.5 % (9/62) at 150 mg/day, and 12.9 % (8/62) at 200 mg/day. Of 33 patients who were seizure-free for ≥24 months at their last study visit, 45.5 % (15/33) started their seizure-free interval on cenobamate doses ≤ 50 mg/day, 3.0 % (1/33) at 100 mg/day, 15.2 % (5/33) at 150 mg/day, and 12.1 % (4/33) at 200 mg/day. CONCLUSION: Of 62/240 patients achieving 12-month seizure freedom at last visit, 35/62 started their seizure-free interval at cenobamate doses ≤200 mg/day (24-month: 25/33). Attaining seizure freedom at a lower dose may be predictive of remaining seizure-free for a longer period. Further prospective research is needed to better define cenobamate's efficacy at lower doses.