Predictors of Sustainability of Response With Cenobamate: Post-hoc Subset Analysis of a Phase 3, Open-Label, Study
Sean Stern, MS1, Robert Wechsler, MD, PhD2, Wesley T. Kerr, MD, PhD3, Clarence T. Wade, MBA1, David G. Vossler, MD4, William E. Rosenfeld, MD5
1SK Life Science, Inc., Paramus, NJ, USA, 2Consultants in Epilepsy & Neurology and Idaho Comprehensive Epilepsy Center, Boise, ID, USA, 3Department of Neurology, University of Michigan, Ann Arbor, MI, USA, 4University of Washington School of Medicine, Seattle, WA, USA, 5Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, MO, USA
Objective:
We evaluated seizure reduction achieved with adjunctive cenobamate and clinical characteristics associated with maintaining response in a post-hoc analysis from a phase 3, open-label, safety study.
Background:
Cenobamate is an antiseizure medication (ASM) approved in the US and EU for the treatment of focal seizures.
Design/Methods:
Patients 18-70 years old with uncontrolled focal seizures taking stable doses of 1-3 ASMs were enrolled. We assessed 100% seizure reduction from baseline achieved over any 3-month interval in the maintenance phase. Loss of response was defined as a visit with seizure reduction <100% vs baseline. Time to 1st and 4th loss of response was the time between onset of response and the patient’s 1st or 4th occurrence of a loss of response, respectively. Logistic regression models were used to evaluate associations with clinical response. Characteristics assessed included sex, race, age, baseline seizure frequency (<3 vs ≥3 seizures/28 days), number of ASMs, use of branded ASMs, presence of secondary generalized tonic-clonic seizures, prior epilepsy-related surgery, and baseline concomitant drug load using defined daily dose (ratios of a patient’s prescribed concomitant ASM doses divided by a standardized daily maintenance dose were summed).
Results:
Of the 214 patients who received ≥1 dose of cenobamate during the maintenance phase (mean age, 41.9 years; median maintenance treatment duration, 29.5 months), 145 (67.8%) had 100% seizure reduction over any 3-month interval. Among patients who initially achieved 100% seizure reduction, the median time to breakthrough seizures was 7 months. Patients with lower baseline concomitant drug load and lower baseline seizure frequency (4th loss only) were more likely to maintain 100% seizure reduction. No other characteristics examined reached significance within the models for 100% seizure reduction.
Conclusions:
In this post-hoc analysis, adjunctive cenobamate led to sustained seizure freedom in patients, including those with characteristics associated with treatment-refractory epilepsy. See also abstract by Wechsler et al.