Cenobamate for Drug-Resistant Epilepsy May Reduce Seizures, Improve Retention

Patients with drug-resistant epilepsy (DRE) treated with cenobamate experience meaningful reductions in seizure frequency and high rates of treatment retention, according to the findings of a study published in Epilepsia Open.

Individuals with DRE face limited options after multiple antiseizure medications (ASMs) fail to provide seizure control. Cenobamate, a recently approved ASM with dual mechanisms, positive GABA-A modulation and sodium channel inhibition, was evaluated as an adjunctive treatment in adults with uncontrolled focal-onset seizures (FOS).

This retrospective, observational cohort included 298 adults (mean age, 37 years; men, 56.7%) with uncontrolled focal seizures who received at least 1 dose of cenobamate between 2020 and 2022 across 19 epilepsy centers. Efficacy outcomes were analyzed in 216 patients with available seizure data.

Baseline characteristics reflected a heavily treatment-experienced population. The median duration of epilepsy was 22.2 years, with a median of 9 previously failed ASMs. Nearly 42% of patients had undergone epilepsy surgery, including vagus nerve stimulation. Intellectual disability was documented in 29.5% of patients, and 26.8% had psychiatric comorbidities.

After 3 months on cenobamate maintenance therapy, 49.3% of patients achieved the primary endpoint of at least a 50% reduction in seizure frequency. Responder rates increased with longer follow-up: 53.2% at 6 months and 60% at 12 months. Complete seizure freedom was achieved in 13.6% of patients at the 3-month mark, increasing to 24.2% at 6 months and 45% at 12 months. The median percentage seizure reduction at 3 months was 49.1%, with higher response rates observed at cenobamate doses ≥200 mg/day.

Retention rates were also favorable, with 96.6% of patients remaining on cenobamate at 1 month, 93.3% at 3 months, and 69.7% at 12 months.

Treatment discontinuation occurred in 12.7% of patients, with adverse drug reactions (ADRs) reported in 30.9%. The most common ADRs were fatigue/asthenia (12.1%), dizziness (6%), and somnolence (5.7%), most of which were mild or moderate and resolved over time. Serious ADRs occurred in 1% of patients, exclusively during the titration phase.

This study was limited by its retrospective design, potential underreporting of seizures or ADRs, and declining patient numbers over time due to the varying duration of Early Access Programs (EAP) participation across countries.

“Our study evidenced that CNB [cenobamate] can be considered generally well tolerated and effective in highly refractory focal or combined generalized and focal epilepsy,” the researchers concluded.

This research was supported by Angelini Pharma. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.