Sustainability of seizure reduction and seizure control with adjunctive cenobamate: Post hoc analysis of a phase 3, open-label study

Objective: In this post hoc analysis of a subset of patients from a long- term, open- label phase 3 study, we assessed = 50%, = 75%, = 90%, and 100% seizure reduc-tion and sustainability of these responses with cenobamate using a time- to- event analytical approach.Methods: Of 240 patients with uncontrolled focal seizures who had adequate seizure data available, 214 completed the 12- week titration phase and received = 1 dose of cenobamate in the maintenance phase (max dose 400 mg/day) and were included in this post hoc analysis. Among patients who met an initial given seizure-reduction level (= 50%, = 75%, = 90%, or 100%), sustainability of that re -sponse was measured using a time- to- event methodology. An event was defined as the occurrence of a study visit at which the seizure frequency during the inter -val since the prior study visit exceeded the initially attained reduction level. Study visits during the maintenance phase occurred at 3- month intervals.Results: Of the 214 patients analyzed, 188 (88%), 177 (83%), 160 (75%), and 145 (68%) met = 50%, = 75%, = 90%, and 100% seizure-reduction responses, respectively, for at least one study visit interval during the maintenance phase. The median (95% confidence interval [CI]) time to first visit without a = 50% seizure reduc-tion was not reached by 30 months of follow- up (53% of patients maintained their initial = 50% seizure reduction). Median (95% CI) time to first visit without sustaining the initial = 75%, = 90%, or 100% seizure reduction was 13.0 (7.5- 21.9) months, 7.5 (5.4- 11.6) months, and 7.0 (5.3- 10.4) months, respectively. Among the 145 patients who had 100% seizure reduction during at least one study visit, 22% remained seizure- free for at least 30 months and 63% had = 3 study visits with seizures.Significance: Adjunctive treatment with cenobamate led to sustained seizure reductions during the maintenance phase of the phase 3 safety study.