Japan Approves Ono's XCOPRI (Cenobamate) for Partial-Onset Seizures After Phase 3 Win
核心洞察
Japan's Ministry of Health, Labour and Welfare approved Ono Pharmaceutical's XCOPRI (cenobamate) tablets on September 16, 2026, for patients with partial-onset seizures (搜索).
Approval was based on the multinational Phase 3 YKP3089C035 trial in South Korea, China and Japan, where all cenobamate doses beat placebo on seizure reduction.
In that trial, cenobamate 400 mg produced a 100% median reduction in seizure frequency during maintenance versus 25.9% for placebo, with 52.4% of patients seizure-free.
Ono Pharmaceutical Co., Ltd. has received manufacturing and marketing approval in Japan for XCOPRI® Tablets (cenobamate) for the treatment of patients with partial-onset seizures (搜索), with or without secondary generalized seizures. The approval, announced September 16, 2026, covers 12.5 mg, 50 mg, 100 mg and 200 mg tablet strengths and makes the anti-seizure medication available in the world's second-largest epilepsy (搜索) market by individual country, where approximately one million people are estimated to have epilepsy.
The approval is based on the randomized, double-blind, placebo-controlled, multinational Phase 3 YKP3089C035 study conducted in South Korea, China and Japan. The trial evaluated XCOPRI as adjunctive therapy in adults aged 18–70 with uncontrolled partial-onset (focal) seizures despite treatment with one to three anti-seizure medications (ASMs). Patients were randomly allocated in a 1:1:1:1 ratio to adjunctive placebo or adjunctive XCOPRI 100, 200 or 400 mg once daily.
All Doses Meet Primary Endpoint
All XCOPRI dosage groups achieved the primary efficacy endpoint, showing a significant reduction in the median percent change in seizure frequency during the 6-week maintenance phase compared with placebo. The median reduction was 25.9% for placebo versus 42.6% for XCOPRI 100 mg, 78.3% for 200 mg and 100% for 400 mg.
On secondary efficacy endpoints, all dosage groups showed significantly higher seizure-free rates than placebo: 2.6% for placebo versus 12.4% for XCOPRI 100 mg, 30.1% for 200 mg and 52.4% for 400 mg. The company noted that the maximum seizure-free rate reported for adjunctive therapy with existing ASMs is around 6.4%, aligning seizure freedom with the overarching goal of epilepsy (搜索) treatment.
The most common adverse events occurring in 20% or more of patients in the XCOPRI groups were dizziness and somnolence. Results of the study were presented in a poster session at the 2024 Annual Meeting of the American Epilepsy (搜索) Society.
Dosing and Mechanism
Under the approved Japanese labeling, the usual adult starting dose is 12.5 mg of cenobamate administered orally once daily. The dose is then increased by one step at intervals of at least two weeks to a maintenance dose of 100 to 200 mg once daily, with adjustment according to the patient's condition. Doses above 200 mg may be increased by 50 mg at intervals of at least two weeks, up to a maximum of 400 mg once daily. The titration schedule to 200 mg proceeds through 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg and 200 mg steps.
Although the precise mechanism by which XCOPRI exerts its therapeutic effects remains unknown, the drug reduces repetitive neuronal firing by inhibiting voltage-dependent sodium currents (搜索) and positively modulates γ-aminobutyric acid type A (GABAA) ion channels.
Unmet Need in Epilepsy
Epilepsy (搜索) is a chronic brain disorder in which seizures are triggered by abnormal excitability of nerve cells in the brain and generally requires long-term drug therapy. According to the source materials, 30% of epilepsy patients do not achieve adequate seizure control with existing ASMs, leaving high unmet medical need for new anti-seizure medications.
As of September 2026, XCOPRI is approved as a treatment for partial-onset seizures (搜索) in more than 45 countries or regions worldwide, including the United States and Europe, where it is marketed as ONTOZRY®. In the United States, SK Biopharmaceuticals' local subsidiary SK Life Science distributes the drug directly, while commercialization in other major markets is conducted through regional partnerships.
Licensing and Ongoing Development in Japan
Ono entered into a licensing agreement with SK Biopharmaceuticals Co., Ltd. (搜索) in 2020, obtaining exclusive rights to develop and commercialize XCOPRI in Japan. SK Biopharmaceuticals originally discovered and developed the anti-seizure medication; the two companies signed a licensing and commercialization agreement for cenobamate in Japan in October 2020. Under the approval, SK Biopharmaceuticals will receive a contractual milestone payment and, in the future, royalties based on Japanese sales.
"With this approval, we have completed the foundation for entering the major Northeast Asian markets of Korea, China, and Japan," said Lee Dong-hoon, CEO of SK Biopharm. "We will now focus on achieving commercialization results that lead to actual patient prescriptions in these markets."
In Japan, Ono is conducting a Phase 3 clinical study of XCOPRI for the treatment of primary generalized tonic-clonic (PGTC) seizures in adolescents and adults, as well as a Phase 3 study in pediatric patients with partial-onset seizures (搜索). SK Biopharmaceuticals and its U.S. subsidiary, SK Life Science Inc., focus on the research, development and commercialization of treatments for central nervous system disorders, with a pipeline that includes seven development compounds for CNS diseases, including epilepsy (搜索), alongside early-stage oncology research.