Long-Term Efficacy and Tolerability of Cenobamate in Clinical Practice: A Retrospective Observational Study

Background and Objectives: Cenobamate (CNB) was approved in the US in 2020 and showed 12% seizure freedom in drug-resistant epilepsy (DRE) in pivotal trials. The open-label extension (OLE) study reported 13%–16% seizure freedom and sustained responder rates over 4 years. It is unclear how much of the treatment benefit during OLE was attributable to CNB, as people could have received other treatments. This study aimed to assess CNB efficacy and safety over an extended follow-up. Methods: This retrospective study was conducted among adults with DRE, treated with CNB between May 2020 and Dec 2023, at the University of California, Davis. Data on demographics, epilepsy history, CNB dose, seizure frequencies, adverse events, and treatment changes were collected. Treatment failure was considered if CNB was withdrawn for any reason or if another epilepsy treatment was needed after starting CNB. Results: Sixty people with epilepsy (PWE) were included, with 78% having focal epilepsy and 11.3% generalized epilepsy. Over the mean follow-up period of 20.5 months, 56.7% had treatment failure, with a median survival time of 17.2 months. Seizure freedom was seen in 15% of participants, and 90% or more seizure reduction in 21% of participants. Of the failures, 44% were due to incomplete efficacy, 38% were due to adverse effects, and the rest due to a combination of both. Seventy-eight percent of PWE who started CNB were taking it at last follow-up. Conclusions: CNB shows clinically meaningful efficacy for at least 1.5 years in people with DRE.