Ono Pharmaceutical Submits Cenobamate Application in Japan Following Successful Phase 3 Trial
核心洞察
Ono Pharmaceutical has submitted a regulatory application for cenobamate (ONO-2017) in Japan for treating partial-onset seizures in adults, based on positive Phase 3 trial results.
The multinational Phase 3 trial demonstrated significant seizure reduction across all cenobamate dose groups, with the 400mg dose achieving 100% median seizure frequency reduction compared to 25.9% for placebo.
Cenobamate showed superior seizure-free rates compared to placebo, with 52.4% of patients in the 400mg group achieving seizure freedom versus only 2.6% in the placebo group.
Ono Pharmaceutical has submitted a regulatory application for cenobamate (ONO-2017) in Japan for the treatment of partial-onset seizures in adults, following successful results from a multinational Phase 3 clinical trial. The submission marks a significant step toward bringing this antiseizure medication to Japanese patients, where approximately 1 million people suffer from epilepsy requiring long-term drug therapy.
Phase 3 Trial Results Demonstrate Superior Efficacy
The YKP3089C035 trial, a randomized, double-blind, placebo-controlled Phase 3 study, evaluated cenobamate's efficacy and safety in adult patients aged 18-70 with uncontrolled partial-onset seizures despite treatment with 1-3 existing antiseizure medications. Conducted across South Korea, China, and Japan, the trial randomly allocated patients to receive either placebo or cenobamate at doses of 100mg, 200mg, or 400mg once daily.
All cenobamate dosage groups achieved the primary efficacy endpoint, demonstrating significant reductions in median seizure frequency during the 6-week maintenance phase. The results showed a dose-dependent response, with placebo achieving a 25.9% reduction compared to 42.6% for cenobamate 100mg, 78.3% for 200mg, and a remarkable 100% reduction for the 400mg dose group.
Seizure-Free Rates Exceed Current Treatment Standards
In secondary efficacy endpoints, cenobamate demonstrated substantially higher seizure-free rates across all dose groups compared to placebo. The seizure-free rates were 2.6% for placebo versus 12.4% for cenobamate 100mg, 30.1% for 200mg, and 52.4% for 400mg. These results are particularly noteworthy given that the maximum rate of seizure-free response in adjunctive therapy with existing antiseizure medications is reported to be around 6.4%.
The most common adverse events occurring in 20% or more of cenobamate-treated patients were dizziness and somnolence. These findings were presented at the 2024 Annual Meeting of the American Epilepsy Society.
Addressing Unmet Medical Needs in Epilepsy
Epilepsy represents a significant medical challenge, with 30% of patients failing to achieve adequate seizure control with existing antiseizure medications. This substantial unmet medical need underscores the importance of new therapeutic options like cenobamate, which has demonstrated high efficacy and the potential to enable more patients to achieve seizure freedom—the primary goal of epilepsy treatment.
Dual Mechanism of Action
Although the detailed mechanism remains unclear, cenobamate reduces repetitive neuronal firing by inhibiting voltage-dependent sodium currents and positively modulates γ-aminobutyric acid type A (GABAA) ion channels. This dual mechanism of action contributes to its therapeutic efficacy in controlling seizures.
Global Commercialization and Partnership
As of September 2025, cenobamate is commercialized as a treatment for partial-onset seizures in 25 countries or regions worldwide, including the United States and Europe. In Japan, Ono obtained exclusive development and commercialization rights through a 2020 licensing agreement with SK Biopharmaceuticals (搜索) Co., Ltd., a South Korean pharmaceutical company focused on central nervous system disorders.
Ono is also conducting a separate Phase 3 clinical trial of cenobamate for treating primary generalized tonic-clonic seizures in adolescents and adults in Japan, potentially expanding the drug's therapeutic applications.
Future Research and Development
SK Life Science (搜索) and SK Biopharmaceuticals (搜索) continue to advance cenobamate research, with plans to present 10 posters featuring new cenobamate data at the 2025 American Epilepsy Society Annual Meeting. These presentations will include long-term efficacy data and early response rates from the open-label extension of the multinational Asian population study, providing additional insights into the drug's clinical profile.