Efficacy and Safety of Adjunctive Cenobamate for the Treatment of Primary Generalized Tonic-Clonic Seizures in Adults and Adolescents
Abstract number :
2.442
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2025
Submission ID :
1354
Source :
www.aesnet.org
Presentation date :
12/7/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Evelyn Shih, MD, PhD – SK Life Science, Inc.
Mark Kristóf Farkas, MD, PhD – Pediatric Center, Semmelweis University
Pavel Klein, MD – Mid-Atlantic Epilepsy and Sleep Center, Bethesda, MD, USA
David Vossler, MD – University of Washington School of Medicine, Seattle, WA, USA
Sunita N Misra, MD – SK Life Science, Inc.
Rationale: Cenobamate is an antiseizure medication (ASM) approved in the US, Europe, and other countries for the treatment of focal seizures in adults at doses of 100-400 mg/d. Preclinical and clinical evidence suggest broad-spectrum antiseizure activity for cenobamate. Here we assess the efficacy and safety of adjunctive cenobamate for the treatment of primary generalized tonic-clonic (PGTC) seizures in patients ≥12 years of age.
Methods: This phase 3, multicenter, randomized, double-blind, placebo-controlled trial (YKP3089C025; NCT03678753) enrolled patients with a clinical diagnosis of PGTC seizures in the setting of idiopathic generalized epilepsy. Patients must have had at least 5 PGTC seizures during the 12-week baseline period (≥1.67 seizures per 28 days) despite treatment with 1-3 ASMs. The double-blind treatment period included a 10-week titration phase and a 12-week maintenance phase. Patients were randomized 1:1 to cenobamate 200 mg/d or matching placebo administered as an oral tablet in adults (≥18 years) or a weight-based equivalent pediatric oral suspension in adolescents (≥12 to < 18 years). Treatment was administered according to the currently approved cenobamate titration regimen for focal seizures (starting at 12.5 mg/d or weight-based equivalent in adolescents) and was titrated to 150 mg/d (or weight-based equivalent) over 10 weeks. Maintenance-phase target cenobamate dose was 200 mg once daily (or weight-based equivalent in adolescents; minimum dose 150 mg/d). Primary efficacy outcomes were median percent change from baseline in 28-day PGTC seizure frequency analyzed in the modified intent to treat (MITT) population (≥1 dose of study drug and ≥1 efficacy measure during double-blind period) and ≥50% responder rates analyzed in the MITT-maintenance (MITT-M) population (≥1 dose of study drug and ≥1 efficacy measure during maintenance phase). Safety and tolerability were also assessed.
Results: Among 169 patients randomized (n=139 adults, mean age, 35 years; n=34 adolescents, mean age 14.3 years), 168 (placebo, n=83; cenobamate, n=85) were included in the MITT population. The MITT-M population included 161 patients (placebo, n=78; cenobamate, n=83). Median percent reduction from baseline in seizure frequency/28 days during the double-blind period was 71.9% for cenobamate (vs 39.6% placebo, P=0.003). Maintenance-phase ≥50% responder rate was 71.1% for cenobamate (vs 51.3% placebo, P=0.01). During the maintenance phase, 43.4% of cenobamate-treated patients were seizure-free (vs 20.5% placebo, P=0.002). Treatment-emergent adverse events (TEAEs) occurred in 53.0% (44/83) of placebo-treated patients and 60.0% (51/85) of cenobamate-treated patients (most commonly somnolence [16.5%] and fatigue [10.6%] for cenobamate). No treatment-related serious adverse events, deaths, or cases of drug reaction with eosinophilia and systemic symptoms (DRESS) were reported.
Conclusions: Adjunctive cenobamate 200 mg/d demonstrated efficacy in treating PGTC seizures in patients ≥12 years of age. These results, taken together with previous preclinical and clinical evidence, suggest that cenobamate is a broad-spectrum ASM.
Funding: Funded by SK Life Science, Inc
Anti-seizure Medications