Long‐term efficacy of adjunctive cenobamate: Open‐label extension of a randomized, placebo‐controlled study in a multinational Asian population

OBJECTIVE: This study was undertaken to assess long-term efficacy, safety, and tolerability of adjunctive cenobamate in an open-label extension (OLE) of a randomized, double-blind, placebo-controlled, dose-response study (NCT04557085; YKP3089C035 [Study C035]) in Asian patients with uncontrolled focal seizures. METHODS: Patients 18-70 years old with uncontrolled focal seizures despite treatment with 1-3 antiseizure medications who completed the 24-week double-blind treatment period (n = 425) at cenobamate doses of 100, 200, or 400 mg/day or placebo could enter a 52-week OLE. All patients were converted to a cenobamate dose of 400 mg/day during a 20-week double-blind conversion phase and then entered a 32-week open-label maintenance phase at a starting dose of 300 mg/day. RESULTS: Among the 410 patients who entered the double-blind conversion phase, 357 (263 and 94 originally randomized to cenobamate and placebo, respectively) entered the OLE maintenance phase. The median percent focal seizure frequency reduction from double-blind baseline for patients who received at least one dose of cenobamate during the 32-week maintenance phase was 83.6%. The percent of patients achieving ≥50% and 100% responses during the maintenance phase was 75.1% and 25.5%, respectively. Among patients entering the OLE, 84.6% (347/410) completed the 52 weeks of treatment with cenobamate. The most commonly occurring treatment-emergent adverse events (TEAEs) during the entire OLE were dizziness, somnolence, γ-glutamyl transferase (GGT) increase, and COVID-19 infection. GGT increase was not associated with any clinically significant findings. Serious TEAEs occurred in 11.7% of patients (48/410). There were no deaths and no cases of DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome reported. SIGNIFICANCE: The high long-term seizure frequency reductions, including a 100% responder rate of 25.5%, were consistent with previous long-term cenobamate efficacy. The OLE safety profile was also generally consistent with the known cenobamate safety profile, with no new safety signals identified. These results support the use of cenobamate in adult Asian patients with uncontrolled focal seizures.