Long-Term Efficacy of Adjunctive Cenobamate by Focal Seizure Subtypes: Open-Label Extension of a Randomized Clinical Study in a Multinational Asian Population
In brief
Cenobamate users had median seizure reductions of 83% to 100% by subtype
In an open-label extension involving 357 Asian adults with difficult-to-control focal seizures, median seizure frequency fell 83% to 100% across three seizure subtypes during maintenance treatment; about three-quarters had at least half as many seizures. Most patients entering the extension completed 52 weeks, but without a control group, the results cannot establish how much of the reduction was due to cenobamate.
- Journal
- Neurology and therapy (Q1)
- Published
- 3 November 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Peimin Yu, Xintong Wu, Ling Chen, Eunyeong Choe, Louis Ferrari, Kyoung Heo, et al.
- PMID
- 42975768
- DOI
- 10.1007/s40120-026-01074-z
Why clinicians should know about it
- Picked for Neurology (clinical) (paper of the day, 6 November 2026): Long-term adjunctive cenobamate outcomes in focal epilepsy
Abstract
INTRODUCTION: To evaluate adjunctive cenobamate efficacy by focal seizure subtype during the open-label extension (OLE) of a phase 3 randomized, double-blind, placebo-controlled study (C035) in Asian patients with focal seizures. METHODS: Patients aged 18-70 years old with uncontrolled focal seizures despite treatment with 1-3 antiseizure medications who completed the double-blind study (n = 425) could enter the 52-week OLE, comprising a 20-week blinded conversion from placebo or 100, 200, or 400 mg/day cenobamate to a target cenobamate dose of 400 mg/day before entering a 32-week open-label maintenance phase at 300 mg/day. Percent change from double-blind baseline in 28-day seizure frequency and responder rates (e.g., ≥ 50% reduction from baseline) for focal preserved consciousness with observable manifestations (FPC), focal impaired consciousness (FIC), or focal to bilateral tonic-clonic (FBTC) seizure subtypes were assessed in the open-label maintenance phase efficacy population (OLE-EM, ≥ 1 dose of study drug and any seizure data during the open-label maintenance phase). Safety and tolerability were assessed. RESULTS: Among patients who entered the OLE, 357/410 (263 originally randomized to cenobamate; 94 who converted from placebo to cenobamate) were included in the OLE-EM population. Median percent seizure frequency reductions were 84.5% for FPC (n = 65), 83.0% for FIC (n = 301), and 100% for FBTC (n = 94) in the OLE-EM population. For FPC, FIC, and FBTC subtypes, ≥ 50% responder rates were 75.4%, 73.8%, and 84.0%, respectively, and 100% responder rates were 23.1%, 28.2%, and 58.5%. Among patients entering the OLE, 84.6% (347/410) completed the 52 weeks of treatment with cenobamate. The most common treatment-emergent adverse events were dizziness, somnolence, gamma-glutamyl transferase increased, and COVID-19 infection. CONCLUSIONS: During the C035 OLE maintenance phase, high seizure frequency reductions were seen for FPC, FIC, and FBTC focal seizure subtypes. Cenobamate was generally well tolerated, and the results were consistent with the double-blind treatment study. Graphical abstract available for this article. TRIAL REGISTRATION: NCT04557085 (registered September 14, 2020).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.