Cenobamate in pediatric drug-resistant epilepsy: real-world evidence from a two-center retrospective study

Epilepsy is common in children and is often manageable. However, only about one-third of individuals remain seizure-free. Drug-resistant epilepsy (DRE) is associated with poor quality of life, an increased risk of sudden death, and adverse neurodevelopmental outcomes. Cenobamate is a new promising antiepileptic drug approved for adults with refractory focal epilepsy, but data from pediatric subjects are limited. This study aims to provide data on cenobamate's use in this population. We performed a two-center retrospective study of pediatric individuals with focal DRE treated with cenobamate as adjunctive therapy, comparing seizure frequency before treatment and after reaching the maximum tolerated dose using routine clinical records. A total of 65 subjects (median age of 11.5 years) were followed for a median of nine months. The median initiation dose was 0.3 mg/kg/day and the median final dose was 2.34 mg/kg/day. At treatment initiation, the participants were receiving a median of 2 anti-seizure medications (IQR: 1 - 3) and had previously been exposed to a median of 5 different medications (IQR: 4 - 7). Twenty individuals had previously been on a ketogenic diet and thirty-two were diagnosed with developmental and epileptic encephalopathy (DEE). Seizure frequency significantly reduced post treatment (p < 0.001): 75% of participants improved, 44.6% had > 50% reduction of seizure episodes and 20% became seizure free. Adverse events were reported in 52.3% of participants, most commonly drowsiness, fatigue, dizziness, ataxia and appetite loss and these were generally mild, well tolerated and mostly self-limiting.

In conclusion, cenobamate appears to be effective and well-tolerated adjunctive therapy in children with DRE, especially in individuals with structural or unknown etiologies.

• Approximately one third of children with epilepsy develop drug-resistant epilepsy. • Cenobamate (CNB) is a novel anti-seizure medication (ASM) used successfully as an adjunctive therapy for refractory focal epilepsy in adults. Only a few studies are available for children.

• This study is one of the limited multicenter studies showing CNB's efficacy and safety in children. • Cenobamate is generally safe and well-tolerated and best responses are observed in individuals with structural abnormalities or epilepsy of unknown etiology, particularly in the absence of developmental and epileptic encephalopathy.