Abstracts

Rationale: The antiseizure medication (ASM) cenobamate has shown efficacy in reducing seizure frequency in adults with uncontrolled focal epilepsy, including those who have had prior epilepsy surgery. Responsive neurostimulation (RNS) electrocorticographic (ECoG) data have been used as a potential method to assess efficacy following the addition of a new ASM. This study assessed the effect of cenobamate on the number of ECoG events recorded by RNS during treatment.

Methods: This retrospective, multicenter, observational, 24-week study included adults (≥18 years) with a history of recurrent focal seizures who initiated adjunctive cenobamate treatment ≥3 months after RNS implant between April 1, 2020 and December 15, 2023. Patients must have had RNS ECoG data for ≥75% of the 8-week baseline (before cenobamate) and 16-week treatment period, and no more than 21 consecutive days of missing RNS data; patients must also have received ≥2 weeks of cenobamate treatment at a minimum dose of 50 mg/day. RNS-detected events (RDE) were obtained from NeuroPace (filters: “long episodes”, “long episodes with saturation”, and “saturation”). RDEs were reviewed to select only epileptiform events (EEs) based on the electrographic ictal pattern. RDEs and EEs were counted during baseline, every 2 weeks for 12 weeks after starting cenobamate, and at the end of the study. The primary outcome was the change in the number of EEs from baseline to the last observation of the treatment period (12+ weeks). Here we present interim data for the first two study sites.

Results: Twenty-seven patients (mean age 35.6 years) were included. At baseline, the median (range) number of RDEs were 23 (1-331) and EEs were 11 (1-275). At baseline, the median (range) number of EEs that were >50 seconds were 5 (0-226) and < 50 seconds were 2 (0-96). There was a significant reduction in the number of EEs averaged over 28 days (53.3%) from baseline to last observation (adjusted pairwise comparison, P< 0.001). Likewise, there were significant reductions in the number of EEs >50 seconds (P≤0.001) and < 50 seconds (P=0.012). 16/27 patients had clinical seizures recorded during baseline and the 16-week treatment period. Among these, there was a 71.6% reduction in clinical seizures per 28 days. Dizziness and lethargy were the most commonly reported adverse events during cenobamate treatment; these resolved with slower titration and/or a lower maintenance dose (100 mg/day). At the last treatment observation, the median (mean) dose of cenobamate was 150 mg (148 mg).

Conclusions: Patients with uncontrolled seizures after RNS had a significant reduction in EEs along with a reduction in clinically reported seizures during adjunctive cenobamate treatment. Results from this interim analysis support the potential use of RNS ECoG data as an objective measure to assess the efficacy of cenobamate and possibly to assess the efficacy of other add-on ASMs.

Funding: Medical writing and submission support funded by SK Life Science, Inc.