Open Label Extension Confirms Cenobamate's Efficacy in Asian Populations

Recently presented positive efficacy data from an ongoing, 52-week open-label extension (OLE) evaluating adjunctive cenobamate (CNB; Xcopri) in multinational Asian patients with uncontrolled focal seizures further validated the drug's broad effectiveness profile. All told, results from the OLE revealed maintained or improved reductions in seizure frequency seen during the original multicenter, randomized, double-blind, placebo-controlled study (YKP3089C035) across all assessed seizure subtypes, depending on randomization group.¹

Presented at the 2025 American Epilepsy Society (AES) Annual Meeting, held December 5-9, in Atlanta, Georgia, the phase 3 study and OLE enrolled male and female Asian adults aged 18-70 (mean age: 35.7 years) who experienced at least 8 focal seizures during an 8-week baseline period despite treatment with 1 to 3 antiseizure medicines (ASMs). Focal seizure subtypes analyzed include focal aware motor (FAM) seizures, focal impaired awareness (FIA) seizures, and focal to bilateral tonic-clonic (FBTC) seizures. For the OLE, 231 patients (50.6% male) entered the extension phase and underwent an 18-week blinded conversion to a target CNB dose of 400 mg/day. Patients (n = 184) then entered the 32-week OLE maintenance phase starting on CNB 300 mg/day (dose 50-400 mg/day).

Led by William E. Rosenfeld, MD, Director at The Comprehensive Epilepsy Care Center for Children and Adults, in St. Louis, Missouri, findings from the OLE maintenance phase showed substantial reductions in median seizure frequency per 28 days from DB baseline across all assessed seizure subtypes. Responder rates during the maintenance phase demonstrated similar benefits with the majority of patients experiencing at least a 50% reduction in seizure frequency.

Overall, responder rates range from about 70% to 78% depending on the subtype. Rates of complete seizure reduction were 19.2% (5/26) for FAM seizures, 29.1% (46/158) for FIA seizures, and 55.6% (25/45) for FBTC seizures. Among the 231 patients in the OLE, the most common treatment emergent adverse events (TEAEs) during the OLE were dizziness, somnolence, and COVID-19 infection.

In the initial phase 3 study, median reductions to 28-day seizure frequency in CNB-treated patients ranged from 48.9%-100% for FAM seizures (vs 26.1% placebo [PBO]) and from 42.6%-100% for focal impaired awareness (FIA) seizures (vs 26.2% PBO). For FBTC seizures, the median seizure frequency reduction was 100% for all CNB dose groups compared to 78.4% with PBO.

Additional data from the phase 3 study revealed that CNB-treated patients experienced median 28-day seizure frequency reductions ranging from 48.9% to 100% for FAM seizures (vs 26.1% with placebo) and from 42.6% to 100% for FIA seizures (vs 26.2% with placebo). For FBTC seizures, all CNB-dosed groups achieved a 100% median reduction compared with 78.4% in the placebo group.

Read more: Cenobamate Data Shows Seizure Reduction, Lower Health Care Use, and Potential SUDEP Risk Reduction

CNB has been previously studied as a treatment for adults with uncontrolled focal onset seizures and demonstrated benefits beyond seizure control. A retrospective analysis of a Spanish cohort from a multicenter, phase 3, open-label study (NCT02535091), showed benefits including decreases in hospitalizations and emergency department visits as well as reductions in sudden unexpected death in epilepsy (SUDEP).^2,3

In the presented analysis, cumulative retention rates were 71%, 60%, and 56% at 1 year, 2 years, and 3 years, respectively. At the final visit, 28.7%, 18.8%, and 11.8% of patients had remained seizure-free for at least 1 year, 2 years, and 3 years, respectively.³ Seizure freedom rates were higher among those who had previously failed 3 or fewer ASMs, underscoring the potential benefit of initiating treatment with effective therapies earlier in the disease course.⁴

REFERENCES
1. Et al. Long-Term Efficacy of AdjunctiveCenobamate by Focal Seizure Subtypes: Open-Label Extension of a Randomized Clinical Study in a Multinational Asian Population . Presented at: 2025 American Epilepsy Society Annual Meeting; December 5-9, Atlanta Georgia.
2. Angelini Pharma Presents Data Demonstrating Benefits of Cenobamate for Adults Living with Uncontrolled Epilepsy. News Release. Angelini Pharma. Published September 1, 2025. Accessed September 8, 2025.
3. Serratosa et al. Efficacy and safety of cenobamate in adults with uncontrolled focal seizures in the Spanish cohort of a Phase 3 open-label clinical trial: a multicenter retrospective study. Presented at: 36th International Epilepsy Conference (IEC); August 31 to September 3, 2025, in Lisbon, Portugal.
4. Lattanzi S. et al. Effectiveness and safety of adjunctive cenobamate in people with focal-onset epilepsy: Interim results after 24-week observational period from the BLESS study. Epilepsia. 2025 Jul;66(7):2239-2252. doi: 10.1111/epi.18357. Epub 2025 Mar 15. August 2025