To assess seizure outcomes, remission rates, and tolerability of cenobamate (CBN) in patients with developmental epileptic encephalopathies within our epilepsy center.

Epileptic encephalopathies (EEs) are among the most severe epilepsy syndromes, which typically require the use of multiple antiseizure medications ASMS) with limited benefit. Cenobamate, a novel sodium channel modulator and positive allosteric modulator of GABA, has shown broad efficacy in focal epilepsy. However, real-world data on its effectiveness and tolerability in patients with epileptic encephalopathies including Lennox Gastaut Syndrome (LGS) remain scarce.

We retrospectively analyzed patients with developmental epileptic encephalopathies (EEs), including LGS, treated with CBN. Seizure frequencies before and after treatment were compared, and response (≥50% reduction) and remission (≥6 months of seizure freedom) rates were recorded. Adverse effects and reasons for discontinuation were also reviewed.

A total of 40 patients (15 females; median age 30.5 [26.8-36]) were included. Mean and median baseline seizure frequency were 38.1 / month; 21 (3.75 – 37.5), respectively. Target dose of 200mg/day was achieved in 30 (75%) patients, and the mean time on CBM was 24.4 months. A significant reduction in seizure frequency was achieved (p < 0.0001), with a drop of mean and median seizure frequencies to 15.1/month and 3.35 (0.7-30), respectively. A responder rate (50% reduction in seizure frequency from baseline) was achieved in 28 (70%) patients. Seizure freedom, defined as being seizure-free for > 6 months, was achieved in 7 (17.5%) of patients. In both univariable and multivariable analyses, baseline seizure frequency was the only predictor of seizure freedom (p = 0.019 and p = 0.045, respectively). A total of 10 (25%) patients stopped CBM, 5 (12.5%) due to lack of efficacy and 5 (12.5%) due to adverse events.

Cenobamate demonstrated meaningful seizure reduction in EEs and LGS, with favorable tolerability.