Cenobamate effective in focal epilepsy

Data from 2 international, double-blind, placebo-controlled trials showed that cenobamate, a voltage-gated sodium channel blocker, has consistent, statistically significant, and clinically meaningful antiepileptic efficacy [1]. Treatment-emergent adverse events (AEs) were dose dependent and generally mild or moderate.

The 2 pivotal trials were named C013 and C017. They enrolled adult patients with uncontrolled focal onset seizures (FOS) with ≥3 seizures per month (C013) or ≥8 seizures per 8 weeks (C017). Participants also used 1-3 concomitant anti-epileptic drugs. In C013 they were randomised to cenobamate 200 mg/day or placebo; in C017 to cenobamate 100, 200, or 400 mg/day, or placebo. Response was defined as ≥50% reduction in seizure frequency from baseline.

In C013, responder rate in the maintenance phase was significantly higher for cenobamate 200 mg versus placebo (62% vs 33%). Seizure freedom rate was significantly higher as well (28% vs 9%). In C017, ≥50% responder rate during maintenance was significantly higher for all cenobamate dosages (100 mg, 40%; 200 mg, 56%; 400 mg, 64%) versus placebo (26%). In the 200 and 400 mg groups, significantly higher rates of patients achieved seizure freedom (11% and 21%, respectively) versus placebo (1%).

There was a significant reduction across all subtypes of FOS in actively treated patients in both C017 (see Figure) and C013, in which reductions in seizure frequency with cenobamate versus placebo in the maintenance phase were:

• Focal aware (91.5% vs 46.5%);
• Focal impaired awareness (62.0% vs 27.6%);
• Focal to bilateral tonic-clonic (100.0% vs 53.0%).

Cenobamate was generally well tolerated. The most frequently occurring AEs (≥10%) were dizziness, somnolence, headache, fatigue, and diplopia.

Figure. Percent reduction in seizure frequency by seizure type in the maintenance phase (C017 study) [1].

1. Steinhoff BJ, et al. Abstract O3006, EAN 2020.

Posted on 9 September 202017 May 2024