Cenobamate for Adjunctive Treatment in Adult and Pediatric Patients with Refractory Lennox-Gastaut Syndrome: A Retrospective Chart Review

Abstract

Introduction: Lennox-Gastaut syndrome (LGS) is a particularly severe developmental epileptic encephalopathy (DEE) characterized by multiple types of drug-resistant, incapacitating seizures. Despite aggressive therapy including polypharmacy, surgery, implanted devices, and dietary therapy, the prognosis remains poor, with frequent ongoing seizures and risk of injury and early death. Cenobamate (CNB) is an antiseizure medication (ASM) approved for the treatment of focal seizures in adults, but real-world experience in patients with DEEs has shown promising reductions in seizure frequency.

Methods: This retrospective chart review determined the effectiveness and tolerability of CNB in 36 adult and pediatric patients with LGS under the treatment of one physician.

Results: Among 36 patients (69% male, median age 15.5 years) with LGS, 86% experienced a reduction in seizure frequency after the addition of CNB (median treatment duration 23 months), including ≥ 75% reduction in 22 patients (61%) and seizure freedom in 5 patients (14%). A substantial proportion of patients (75%, n = 27) successfully reduced their concomitant medications, including the lowering or discontinuation of cannabidiol in 19 patients and clobazam in 21 patients. Adverse events were reported in two-thirds of patients, reflecting the same symptoms reported in the original approval trials, with somnolence being the most common.

Conclusions: This chart review provides promising evidence for the efficacy of CNB in treating LGS. Additional prospective studies will help to clarify CNB's efficacy and safety profile for patients with LGS.

Keywords: Cenobamate; Lennox–Gastaut syndrome; Pharmacotherapy; Refractory epilepsy.

Fig. 1

Seizure response rates during treatment with cenobamate