Abstracts

Rationale: The definition of drug-resistant epilepsy (DRE) is failure of at least two anti-seizure medications (ASMs) at appropriate doses and appropriate time of trial, with good tolerability to achieve seizure freedom. Cenobamate (CNB) is a new anti-seizure medication (ASM) approved for the treatment of focal seizures in adults. The efficacy of CNB has been previously demonstrated in two phase-II randomized double-blind controlled trials (RCT), which reported seizure freedom in 21-28% of patients with DRE. We report a post-marketing multi-center experience of CNB in a cohort of patients with drug-resistant epilepsy.

Methods: We conducted a two-center retrospective study of adults diagnosed with DRE who were treated with CNB between 2020 and 2024 at the George Washington University Hospital (GWUH) and Vanderbilt University Medical Center (VUMC). Institutional review board approval was granted from the two centers. Descriptive analysis was utilized to summarize the characteristics of the study population and the main outcome measures. Continuous variables are presented as means with their respective standard deviations, and categorical variables are presented as percentages.

Results: CNB was prescribed to 121 patients (52 women) between 2020 and 2024. The efficacy analysis included a total of 104 patients and the tolerability analysis was comprised of 111 patients. The mean age at presentation was 41.9 years. The number of concomitant medications at baseline was 2.2 (±0.9). Baseline seizure frequency was 20.36 (±65.4) per 3 months. Duration of follow-up ranged between 3 and 37 months. Most patients (95.3%) had an EEG recording done that provided detailed characterization of their epilepsy type. Forty-six (44.2%) patients had a lesional MRI finding. The mean doses reached at 3,6,9 and 12 months are 158.2 mg, 186.82 mg, 217.91 mg, and 235.78 mg. The lowest proportion of patients receiving concomitant medications was at 12 months. The number of patients at 3,6,9, and 12 months follow-up was 104 (100%), 78 (75%), 62 (59.6%), and 49 (47.1%), respectively. The highest percentage responder rates were at 12 months. Thirty-six (34.6%) patients became completely seizure free, with a mean duration of seizure freedom of 11 (± 7.9) months. A total of 45 (42.8%) patients experienced adverse events, with drowsiness (13, 27%) and fatigue (11, 23%) being the two most common.



Conclusions: CNB use in a large population of more than 100 patients demonstrated impressive anti-seizure activity with a good proportion of patients with drug-resistant epilepsy achieving seizure freedom despite having failed multiple prior ASMs. In addition, CNB offered an attractive safety profile with relatively low rates of discontinuation. We suggest modifying the definition of drug-resistant epilepsy to include CNB as one of two ASMs failing to achieve seizure control.

Funding: No funding was received in support of this abstract