Abstracts

Rationale: To assess the safety and efficacy of cenobamate (CNB) as adjunctive therapy in adult patients with focal onset seizures participating in an early access program.

Methods: We prospectively recorded information from all adult patients with focal epilepsy who were treated with at least a single dose of CNB as adjunctive therapy in an early access program. Most patients did not meet criteria to be included in clinical trials. These were well studied, highly refractory patients in whom seizure-freedom could not be reasonably expected due to a previous history of lack of response to most or all available anti-seizure medications (ASM). We analyzed adverse effects at 3 and 6 months, 50% and 90% responder and seizure-free rates at 6 and 12 months (4- 6 month and 4- 12 month evaluation periods respectively) and retention rates at 6 and 12 months. Baseline seizure frequency was measured during a 3-month period prior to CNB initiation. We considered seizure freedom as the absence of focal aware seizures with a motor or observable component, focal unaware seizures or focal to bilateral tonic-clonic seizures during the whole evaluation period.

Results: Fifty-one patients older than 18 years with drug-resistant focal epilepsy were included. Mean duration of epilepsy: 12,9 years (from birth to 49 years); Mean seizure frequency during the 3-month baseline period: 24,5 seizures/month (median: 6 seizures/month); Median number of previous antiseizure medications (ASM): 8; Median number of concomitant ASM: 3 (sodium channel blockers: 47/51 patients, benzodiazepines: 32/51 patients); Mean dose at last visit: 251,22 mg/day (range: 100-400 mg/day). Six-month >50% and >90% responder rates were 41,2% (14/34 patients) and 20,6% (7/34 patients) respectively and 1/34 patients was seizure-free. At 6 months, 34/40 patients continued on CNB (retention rate: 85%). Twelve-month >50% and >90% responder rates were 46,7% (7/15 patients) and 33,3% (5/15 patients) respectively and no patient was seizure-free. At 12 months 15/20 patients continued on CNB (retention rate: 75%). Adverse effects (AEs) were experienced by 34/51 patients during the 3-month titration period and by 30/34 patients during the whole 6- month period. The most common AEs were somnolence and unsteadiness. One patient had a skin rash without systemic symptoms resulting in drug withdrawal. At the time data for this work was recorded, 10 of the 51 patients had discontinued CNB (4 due to AEs, 3 due to lack of efficacy, and 3 due to both).

Conclusions: In our series of patients with super-refractory focal epilepsy, CNB showed high efficacy as adjunctive therapy. Retention rates were high at 6 and 12 months. AEs were those commonly observed with other ASM and led to withdrawal of CNB in 13,7% of the patients.

Funding: None