Abstracts

Rationale: Cenobamate is an antiseizure medication (ASM) approved in the U.S. and EU for the treatment of adults with focal seizures. Drug-resistant epilepsy is defined by the absence of seizure freedom despite trials of ≥ 2 appropriately selected and tolerated ASMs. In this post-hoc analysis, we evaluated if clinical characteristics could predict a meaningful response to cenobamate prior to initiation using data from a phase 3, open-label, safety study (C021). The ability to predict a high likelihood of seizure freedom with cenobamate treatment could help with clinical selection of ASMs.

Methods: Patients 18 to 70 years old with uncontrolled focal seizures taking stable doses of 1 to 3 ASMs were enrolled in the C021 study. In the 13-week baseline period prior to screening, patients had to have ≥ 1 focal aware motor, focal impaired awareness, or focal to bilateral tonic-clonic seizure. To perform post-hoc analyses, seizure data were collected from 10 study sites that enrolled ≥ 11 patients who received ≥ 1 dose of cenobamate and had systematically captured high-quality seizure data. For patients who completed the 12-week titration phase and received ≥ 1 dose of adjunctive cenobamate in the maintenance phase, we assessed ≥ 50% and 100% seizure reduction from baseline achieved over any 3-month interval. Baseline demographics and clinical characteristics assessed included: sex, race, age, baseline seizure frequency (< 3 seizures versus ≥ 3 seizures), number of ASMs, use of branded ASMs, presence of secondary generalized tonic-clonic seizures, duration of epilepsy, prior epilepsy-related surgery, and baseline concomitant drug load measured using defined daily dose (drug load was calculated by summing the ratios of a patient’s prescribed ASM doses divided by a standardized daily maintenance dose). We used multivariable logistic regression to evaluate associations with either level of clinical response.

Results: Data from 214 patients with a mean age of 41.9 years and a median duration of cenobamate treatment during the maintenance phase of 29.5 months were analyzed. Of these 214 patients, 188 (87.9%) and 145 (67.8%) achieved ≥ 50% and 100% seizure reduction, respectively, over any 3-month interval. Lower baseline concomitant drug load was significantly associated with a higher likelihood of achieving ≥ 50% and 100% seizure reduction (p < 0.05) (Table 1). Lower baseline seizure frequency was significantly associated with a higher likelihood of achieving 100% seizure reduction (p < 0.05) (Table 2). None of the other baseline demographics or clinical characteristics analyzed achieved significance.