Efficacy of Cenobamate for Uncontrolled Focal Seizures: Post-hoc Analysis of a Phase 3, Multicenter, Open-Label Study
Michael R. Sperling1, Bassel Abou-Khalil2, Sami Aboumatar3, Perminder Bhatia4, Victor Biton5, Pavel Klein6, Gregory L. Krauss7, David G. Vossler8, Robert Wechsler9,10, Louis Ferrari11, Marc Kamin11, Mindy Grall11, William E. Rosenfeld12
1Thomas Jefferson University, 2Vanderbilt University, 3Austin Epilepsy Care Center, 4Neuro Pain Medical Center, 5Arkansas Epilepsy Program, 6Mid-Atlantic Epilepsy and Sleep Center, 7Johns Hopkins University, 8University of Washington School of Medicine, 9Consultants in Epilepsy & Neurology, 10Idaho Comprehensive Epilepsy Center, 11SK Life Science, Inc., 12Comprehensive Epilepsy Care Center for Children and Adults
Objective:

Report post-hoc efficacy data from 10 US study sites from the long-term, global, open-label phase 3 safety study.

Background:
Cenobamate is an antiseizure medication (ASM) approved in the US for the treatment of adults with focal seizures.
Design/Methods:
Patients 18-70 years old with uncontrolled focal seizures taking stable doses of 1-3 ASMs were administered increasing daily doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) over 12 weeks at 2-week intervals to a target dose of 200 mg/day. Further increases to 400 mg/day by 50-mg/day increments every other week were allowed during the maintenance phase. Dose adjustments of cenobamate and concomitant ASMs were allowed.
Results:
Two hundred forty patients with focal aware motor, focal impaired awareness, or focal to bilateral tonic-clonic seizure data while on treatment were evaluated (median duration of exposure 30.2 months). Mean baseline seizure frequency/28 days was 18.1 seizures/28 days (median 2.8). Of the 240 patients, 25.8% (62/240) had 100% seizure reduction for ≥12 months at the last visit; 36.3% (87/240) had 100% seizure reduction for ≥12 months at any visit. 100% seizure reduction durations of ≥6 and ≥3 months occurred in 35.0% (84/240) and 44.6% (107/240) of patients, respectively, at the last visit. Of the 240 patients, 177 (73.8%) were continuing on cenobamate at the last visit, and 60/177 (33.9%) had 100% seizure reduction for ≥12 months at the last visit. During the entire maintenance phase (maintenance population, n=214), ≥50%, ≥75%, ≥90%, and 100% responder rates occurred in 75.7% (162/214), 57.5% (123/214), 40.2 (86/214), and 13.6% (29/214) of patients, respectively. Most common adverse events among all patients included fatigue, dizziness, and somnolence.
Conclusions:
High rates of sustained 100% seizure reduction (≥12 months) were achieved with cenobamate in this post-hoc analysis from the long-term open-label study, further supporting durable seizure frequency reduction with cenobamate in adults with uncontrolled focal seizures.