Adjunctive treatment with cenobamate produces significant reductions in seizures compared with a placebo, according to a study published in The Lancet Neurology. The study examined the safety and efficacy of cenobamate, an investigational anti-epileptic drug (AED) in patients with uncontrolled focal (partial onset) seizures.

More than one-third of patients with epilepsy are treatment resistant. Therefore, researchers wanted to find a more effective treatment option. Cenobamate is an investigational antiepileptic drug that has shown broad-spectrum anticonvulsant activity in preclinical studies and seizure models, according to a press release.

In the multicenter, double-blind, randomized, placebo-controlled, dose-response study, researchers randomized eligible patients who were taking 1 to 3 AEDs to either once daily placebo or cenobamate 100 mg, 200 mg, or 400 mg and treated them for 18 weeks. Patients, investigators, and study personnel were masked to treatment assignment.

The study included a 6-week titration phase and 12-week maintenance phase. The primary outcomes surrounding efficacy were percentage change in 28-day focal seizure frequency from baseline analyzed in the modified intention-to-treat population and responder rates analyzed in the maintenance phase population.

The findings suggest that there was a statistically significant greater median percent reduction in focal seizure frequency over the entire treatment period compared with baseline for the cenobamate 100 mg, 200 mg, and 400 mg (36%, 55% and 55%, respectively) cohorts compared with the placebo group (24%). Additionally, a statistically significant greater percentage of patients achieved a 50% or higher reduction in focal seizures during the maintenance phase compared with baseline for the cenobamate 100 mg, 200 mg, and 400 mg groups (40%, 56% and 64%, respectively) compared with the placebo group (25%).

Additionally, 4%, 11%, and 21% of patients treated with cenobamate 100 mg, 200 mg, and 400 mg, respectively, reported no focal seizures compared with only 1% of patients who were treated with a placebo, according to the press release.

“More than one-third of patients with epilepsy have uncontrolled seizures and treatment outcomes for these patients have not substantially improved over the past 20 years. Based on the results in the maintenance phase of the study, a post-hoc analysis of the number of patients needed to treat to get someone to zero focal seizures was 10 for the 200 mg dose and five for the 400 mg dose. We are encouraged by these results as they suggest that cenobamate may be able to help patients with focal seizures who have not yet achieved adequate seizure control,” said Marc Kamin, MD, chief medical officer of SK Life Science, Inc.

The most common most treatment-emergent adverse events (TEAEs) reported were sleepiness, dizziness, headache, fatigue, and diplopia (double vision), the incidences of which increased with the dosage. Overall, the TEAEs were mild or moderate in severity and similar to those observed with other AEDs. One serious case of drug reaction with eosinophilia and systemic symptoms occurred in the 200 mg cenobamate group.