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

David G Vossler; William E Rosenfeld; Sean Stern; Clarence T Wade; Louis Ferrari; Wesley T Kerr; Robert Wechsler

doi:10.1111/epi.17724

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

Epilepsia. 2023 Oct;64(10):2644-2652. doi: 10.1111/epi.17724. Epub 2023 Aug 7.

Authors

David G Vossler¹, William E Rosenfeld², Sean Stern³, Clarence T Wade³, Louis Ferrari³, Wesley T Kerr⁴, Robert Wechsler⁵

Affiliations

¹ University of Washington School of Medicine, Seattle, Washington, USA.
² Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, Missouri, USA.
³ SK Life Science Inc., Paramus, New Jersey, USA.
⁴ Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
⁵ Consultants in Epilepsy & Neurology and Idaho Comprehensive Epilepsy Center, Boise, Idaho, USA.

PMID: 37497579
DOI: 10.1111/epi.17724

Abstract

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 reduction 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 response 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 interval 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 reduction 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.

Keywords: cenobamate; epilepsy; focal seizures; seizure control; sustainable response.