In the phase 2 trial (NCT01866111) treatment with cenobamate (SK Life Science, Paramus, NJ) resulted in statistically significant greater reductions in focal seizure frequency compared with baseline. Those treated with cenobamate 100 mg, 200 mg, and 400 mg had median seizure frequency reduction of 36%, 55%, and 55%, respectively, compared with the placebo group (24%). Those doses also resulted in a 50% or more reduction in focal seizures compared with baseline during the maintenance phase (40%, 56%, and 64%) vs placebo (25%). During the maintenance phase, 4%, 11%, and 21% of participants treated with cenobamate 100 mg, 200 mg, and 400 mg reported no focal seizures compared with only 1% of placebo-treated participants.
Most treatment-emergent adverse events (TEAEs) were mild or moderate in severity, and similar to those observed with other anti-epileptic drugs (AEDs). The most common TEAEs reported were somnolence, dizziness, headache, fatigue, and diplopia, and the incidences increased with dosage. A serious case of drug reaction with eosinophilia and systemic symptoms (DRESS) occurred a person treated with 200 mg cenobamate.
"This is the first publication showing the results of a randomized, controlled clinical trial of cenobamate in adults with uncontrolled focal seizures," said Gregory L. Krauss, MD, professor of neurology at Johns Hopkins University and lead author of the study. "The results demonstrated significant dose-related reductions in seizure frequency with cenobamate during the maintenance phase compared to placebo. Encouragingly, a high number of patients had 0 seizures during the maintenance phase in the 200 mg and 400 mg groups."
"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," said Marc Kamin, MD, chief medical officer, SK Life Science. "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 0 focal seizures was 10 for the 200 mg dose and 5 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."
The trial was a multicenter double-blind randomized placebo-controlled dose-response study of the safety and efficacy of cenobamate in adults with uncontrolled focal (partial-onset) seizures. Eligible participants taking 1 to 3 AEDs were randomly assigned to treatment with once-daily placebo or cenobamate 100 mg, 200 mg, or 400 mg and treated for 18-weeks. A 6-week titration phase was followed by a 12-week maintenance phase at the target dose.
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