Ono Pharmaceutical has received manufacturing and marketing approval of XCOPRI (cenobamate) Tablets 12.5 mg, 50 mg, 100 mg, 200 mg (XCOPRI) for the treatment of patients with partial-onset seizures, with or without secondary generalised seizures.

This approval is based on the results of a multinational phase 3 clinical study (YKP3089C035) conducted in Asian patients with uncontrolled partial-onset (focal) seizures despite treatment with antiseizure medications (ASMs). In this study, adjunctive therapy with XCOPRI showed a statistically significant improvement in the median percent change in seizure frequency, the primary endpoint, compared with existing treatment alone. A manageable safety profile was also observed.

YKP3089C035 was a randomised, double-blind, placebo-controlled, multinational phase 3 clinical study conducted in South Korea, China, and Japan. In this study, the efficacy and safety of XCOPRI as adjunctive therapy was evaluated in adult patients aged 18 to 70 years with uncontrolled partial-onset (focal) seizures on 1-3 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 dosage groups of XCOPRI 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 the placebo group. XCOPRI 400 mg group showed a 100 percent reduction in the median seizure frequency during the maintenance period (placebo: 25.9 percent vs XCOPRI: 42.6 percent for 100 mg, 78.3 percent for 200 mg, and 100 percent for 400 mg).

In the secondary endpoints for efficacy, all dosage groups of XCOPRI showed significantly higher seizure-free rate compared with the placebo group (placebo: 2.6 percent vs XCOPRI: 12.4 percent for 100 mg, 30.1 percent for 200 mg, and 52.4 percent for 400 mg). The most common adverse events with the incidence of 20 percent or more in XCOPRI groups were dizziness and somnolence.

The results of this study were presented in a poster session at the 2024 Annual Meeting of the American Epilepsy Society (AES).

The maximum rate of seizure-free, which aligns with the goal in epilepsy treatment, in adjunctive therapy with existing ASMs is reported to be around 6.4 percent.