Abstracts

Rationale: In addition to transiently reducing seizure frequency, the ability of an antiseizure medication (ASM) to maintain a response beyond the 3-month clinical trial observation window can be critical to improving quality of life for patients with epilepsy. In this post-hoc analysis of a phase 3, open-label, safety study (C021), we evaluated the duration of seizure reduction achieved with adjunctive cenobamate and clinical characteristics that were associated with maintenance of response.

Methods: Patients 18 to 70 years old with uncontrolled focal seizures taking stable doses of 1 to 3 ASMs were enrolled in the C021 trial. Seizure data for post-hoc analyses were collected from 10 study sites that enrolled ≥ 11 patients who received ≥ 1 dose of cenobamate and had recorded high-quality seizure data. Patients who had a ≥ 50% or 100% seizure reduction response for ≥ 3 months in the maintenance phase of the C021 trial were included in this post-hoc analysis. Loss of response was defined as a visit with seizure reduction of < 50% or < 100% vs. baseline and was used to measure maintenance of response. Time to first and fourth loss of response was the time between the onset of response and the patient’s 1st or 4th occurrence of a loss of response, respectively. Cox-proportional hazards with censoring were used to evaluate associations with maintenance of response. Clinical characteristics assessed included: sex, race, age, baseline seizure frequency (< 3 seizures vs ≥ 3 seizures), number of ASMs, use of branded ASMs, presence of secondary generalized tonic-clonic seizures, 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 concomitant ASM doses divided by a standardized daily maintenance dose).

Results: Of the 214 eligible patients (mean age, 41.9 years; median duration of cenobamate treatment during the maintenance phase, 29.5 months), 188 (87.9%) and 145 (67.8%) had ≥ 50% and 100% seizure reduction, respectively, for ≥ 3 months. More than half of patients maintained their initial ≥ 50% and 100% seizure reduction response for > 30 months and 6.9 months, respectively. Lower baseline concomitant drug load and shorter duration of epilepsy were associated with longer times to first loss of ≥ 50% seizure reduction (p < 0.05) (Table 1). Lower baseline concomitant drug load and seizure frequency (fourth loss only) were associated with longer times to first and fourth loss of 100% seizure reduction (p < 0.05) (Table 2). No other clinical characteristics examined reached significance.