Bial has announced that the European Medicines Agency (EMA) will review recent clinical trial data for Zebinix (eslicarbazepine acetate) as a once-daily treatment for patients suffering from newly diagnosed epilepsy. The results of the clinical trial were initially presented at the Academy of Neurology Annual Meeting in April.
Partial-onset or focal seizures occur frequently among patients who suffer from epilepsy. In Europe, Zebinix is recommended for the treatment of partial-onset seizure as an adjunctive therapy in people who experience secondary generalization. In the U.S., Aptiom is recommended either as a monotherapy or as an adjunctive therapy.
Eslicarbazepine acetate, the active agent of Zebinix, is a voltage-gated sodium channel blocker, which selectively targets the slow inactivated state of the ion channel, and is able to block sodium flow into the nerve cells in the brain, reducing the activity of the nerve cells, the intensity, and the number of seizures.
“It is a significant milestone in Bial’s commitment to help people who live with epilepsy,” said António Portela, CEO of Bial, about the EMA submission. “We have been developing eslicarbazepine acetate for many years and it’s very encouraging to have the monotherapy submission acceptance. We hope it will become available for those living with epilepsy and for those who manage the condition.”
The Bial-supported Phase 3 study included adult patients who had partial-onset seizures. The study showed that monotherapy is as effective as the current standard method, the controlled-release carbamazepine.
The clinical study was a randomized, double-blind, parallel-group, active-controlled and non-inferiority study. The efficacy and safety of Zebinix taken once a day (800 to 1600 mg daily) as monotherapy was investigated in patients with partial-onset seizures. The results were compared to the observations of a twice-daily controlled-release carbamazepine (400 to 1,200 mg daily) therapy. The primary endpoint was the ratio of seizure-free patients over 26 weeks. Secondary endpoints involved the time until the first seizure, a QOLIE-31 quality of life assessment, and safety.
Efficacy analysis with 785 eligible patients revealed that patients treated with Zebinix had seizure-free rates of 71 percent and 75.6 percent with controlled-release carbamazepine after six months. The seizure-free rate was 64.7 percent in the Zebinix group and 70.3 percent in the controlled-release carbamazepine group for a one-year period.
A safety analysis with 813 eligible people demonstrated that Zebinix taken once a day is well tolerated, and side effects are mild to moderate. Incidence rates of treatment emergent adverse events (TEAEs) were similar but somewhat lower in patients treated with Zebinix (77.8 percent) versus patients treated with controlled-release carbamazepine (80.1 percent).
Serious treatment-related TEAEs in patients treated with Zebinix versus patients treated with controlled-release carbamazepine were 2.0 percent vs 2.7 percent, and for TEAEs leading to withdrawal were 13.5 percent vs 18 percent. The most frequent TEAEs were headache, dizziness, nausea, fatigue, and somnolence.