According to a commentary, a third of patients with epilepsy worldwide are in need of more effective anticonvulsive drugs, since their epileptic seizures remain uncontrolled with currently available medical treatments. It notes the mechanism of action of this drug is still under investigation. Besides inhibiting excitatory sodium-channel currents, it is believed that cenobamate enhances inhibition by modulation of GABAA receptors.
It highlights that a remarkable finding from the post-hoc analysis is the high percentage of patients with 100% seizure control during the 12-week maintenance phase of this study. Specifically, 20 (21%) of 95 patients treated with cenobamate at 400 mg/day and 11 (11%) of 98 patients treated with cenobamate at 200 mg/day had no seizures during the 12-week maintenance phase, vs. one patient (1%) on placebo. The commentator adds that to his knowledge, a seizure freedom rate of 20% or higher has not yet been reported in a placebo-controlled, double-blind trial of anticonvulsive drugs. Furthermore, the high efficacy of cenobamate found in the two phase 2 clinical trials led to the decision of FDA that no additional efficacy studies were needed, and subsequent phase 3 trial is focusing on safety measures. The rate of up-titration of cenobamate was regarded to be crucial for the risk of allergic drug reactions, and this trial is testing a reduced starting dose of cenobamate at 12·5 mg/day and a slow up-titration scheme (25 mg, 50 mg, 100 mg, 150 mg, and 200 mg at 2-week intervals; further stepwise dose increments up to 400 mg/day were allowed).
The commentary acknowledges limitations of phase 2 and 3 trials: patients are highly selected for enrolment, depending on the inclusion and exclusion criteria, the maintenance phase typically has a short duration, and the dosage of concomitant drugs must be kept unchanged throughout the study. Therefore future findings under real-life conditions will reveal the clinical relevance of cenobamate.
A new drug application for cenobamatye is sitting with the FDA and plans for a marketing authorisation application in Europe are in progress.