Baldwin Keyes Professor of Neurology Thomas Jefferson University Philadelphia, Pennsylvania
Rationale: Cenobamate is an antiseizure medication (ASM) approved in the U.S. for the treatment of adults with focal seizures. Approval of cenobamate was based on efficacy and safety data from two Phase 2 studies and safety data from a long-term, ongoing, open-label Phase 3 safety study. Here, we report post-hoc efficacy data from ten U.S. study sites from the global Phase 3 study. Methods: Patients 18-70 years old with uncontrolled focal seizures taking stable doses of one to three ASMs were enrolled. Increasing daily doses of cenobamate were administered (12.5, 25, 50, 100, 150, and 200 mg/day) at two-week intervals. Further increases to 400 mg/day by 50-mg/day increments every other week were allowed. Patient visits occurred every two weeks for 16 weeks and then every one to three months. Adjustments to concomitant ASMs were allowed during the study. Cenobamate monotherapy was not allowed. Focal aware motor, focal impaired awareness, and focal to bilateral tonic-clonic (FBTC) seizures were assessed post-hoc. Results: Efficacy data were available for 249 of the total 1,347 patients enrolled. Of the 249 patients, 183 (73.5%) were still on cenobamate as of the last three-month clinic visit (mean duration 33.9 months). Mean seizure frequency at screening was 10.7 seizures/28 days (range: 0.31-140 seizures/28 days). Of the 183 patients still on cenobamate, 62 (33.9%) were seizure-free for ≥12 months at the last 3-month visit (Figure 1), with a mean seizure-free duration of 23.6 months (range: 11.5 to 39.5 months). For these 62 patients, the median dose of cenobamate was 200 mg/day (mean dose 251.6 mg/day). Seizure-free durations of ≥6 and ≥3 months occurred in 43.2% (79/183) and 54.6% (100/183) of patients still on cenobamate, respectively, as of the last 3-month visit. Any seizure-free duration (i.e., not just at last visit) of ≥12 months occurred in 45.9% (84/183) of patients still on cenobamate; mean seizure-free duration was 22.9 months (range: 11.5-39.5 months). For all 249 patients, 64 (25.7%) were seizure-free ≥12 months at last visit, with a mean seizure-free duration of 23.5 months (range: 11.5-39.5 months). Seizure-free durations of ≥6 and ≥3 months occurred in 34.5% (86/249) and 44.2% (110/249) of all patients, respectively, at last visit. Any seizure-free duration of ≥12 months occurred in 34.5% (86/249) of all patients. After excluding patients who had < 1 FBTC seizure/year or missing data, responder rates were evaluated in 173 of the 183 patients still on cenobamate (Figure 2). Compared to screening, ≥50%, ≥75%, and 100% responder rates were 85.0% (147/173), 74.0% (128/173), and 57.2% (99/173), respectively, in the last three months. The most common adverse events included dizziness/diplopia and sleepiness/drowsiness. Conclusions: High rates of sustained seizure-freedom (≥12 months) were achieved with cenobamate in this post-hoc analysis from an ongoing, long-term phase 3 open-label study, further supporting the durable reduction in seizure frequency with cenobamate in adult patients with uncontrolled focal seizures. Funding: Please list any funding that was received in support of this abstract.:
