Seizure-free days as a clinical outcome measure of reduced epilepsy burden: 5-year outcomes with cenobamate treatment

Background: Sustained seizure freedom without intolerable adverse events is the main goal of epilepsy treatment, but may be challenging to achieve for some patients, particularly following the failure of multiple anti-seizure medications (ASMs). A majority of days without seizures is another important clinical outcome that can lead to meaningful improvement in quality of life. The objective of this post-hoc analysis was to evaluate the percentage of seizure-free days by responder groups during the open-label extension (OLE) of study C017 with a focus on patients who achieved near-seizure freedom that was sustained during the duration of the study (= 90%-< 100% responders group). The study also evaluated retention rates and the impact of concomitant antiseizure medications. Methods: Study C017 (NCT01866111) was a double-blind, randomized, placebo-controlled, dose–response trial evaluating adults 18–70 years old who were taking 1–3 concomitant ASMs. Participants completed the 18-week double-blind treatment period and entered the OLE. This post-hoc analysis quantified the proportion of seizure-free days by responder category and by number and type of concomitant ASMs. The occurrence and severity of treatment-emergent adverse events during the OLE were also reported. Results: Sixty (16.9%) of the 354 study participants were = 90%-< 100% responders (median age 42.5 years, 46.7% [n = 28] female, median number of concomitant ASMs at baseline was 2). The study population also included 91 (25.7%) patients who were = 50%-< 75% responders, 62 (17.5%) patients who were = 75%-< 90% responders, and 13 (3.7%) patients who were 100% responders. The median duration of cenobamate exposure was 5.6 years for the = 90%-< 100% responders; 1.8 years for the non-responders; 5.5 years for the = 50%-< 75% responders; 5.5 years for the = 75%-< 90% responders; and 5.6 years for the 100% responders. The percentage of seizure-free days during the entire OLE was 97.9% in the = 90%-< 100% responder group, compared to 93.5% in the = 75%-< 90% group and 83.9% in the = 50%-< 75% group. The number and mechanism of action of concomitant ASMs did not meaningfully impact the proportion of days without seizures. The percentage of days with seizures in the = 90%-< 100% responder group declined from 33.2% at baseline to 1.2% at Year 5. At Year 5, the = 90%-< 100% responder group had a high retention rate (90%). The most commonly occurring adverse events were dizziness, somnolence, and headache. Conclusions: Participants taking cenobamate who achieved = 90%-< 100% responder rates were seizure-free for nearly 98% of days during the 5 years of the OLE. These results suggest that a high reduction of seizure burden can be achieved and maintained by many people with epilepsy taking cenobamate. © 2026 The Authors