Predictors of Achievement of Response With Cenobamate: Post-hoc Subset Analysis From a Phase 3, Open-Label Safety Study
Robert Wechsler, MD, PhD1, David G. Vossler, MD2, Wesley T. Kerr, MD, PhD3, Sean Stern, MS4, Clarence T. Wade, MBA4, William E. Rosenfeld, MD5
1Consultants in Epilepsy & Neurology and Idaho Comprehensive Epilepsy Center, Boise, ID, USA, 2University of Washington School of Medicine, Seattle, WA, USA, 3Department of Neurology, University of Michigan, Ann Arbor, MI, USA, 4SK Life Science, Inc., Paramus, NJ, USA, 5Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, MO, USA
Objective:
We evaluated post-hoc whether clinical characteristics could predict a meaningful response to cenobamate in a subset of patients from a phase 3, multicenter, open-label, safety study.
Background:
The ability to predict a high likelihood of seizure freedom with cenobamate treatment could help with clinical antiseizure medication (ASM) selection.
Design/Methods:
Patients 18-70 years old with uncontrolled focal seizures taking stable doses of 1-3 ASMs were enrolled. For patients who completed the 12-week titration phase and received ≥1 dose of adjunctive cenobamate in the maintenance phase, we assessed ≥50% and 100% seizure reduction from baseline achieved over any 3-month interval. Various baseline demographics and clinical characteristics were assessed, including concomitant drug load measured using defined daily dose (drug load was calculated by summing the ratios of a patient’s prescribed ASM doses divided by a standardized daily maintenance dose). We used multivariable logistic regression to evaluate associations with clinical response.
Results:
Data from 214 patients (mean age 41.9 years; median duration of maintenance treatment 29.5 months) were analyzed. Of these patients, 188 (87.9%) and 145 (67.8%) achieved ≥50% and 100% seizure reduction, respectively, over any 3-month interval. Lower baseline concomitant drug load was significantly associated with a higher likelihood of achieving ≥50% (P=0.0410) and 100% (P=0.0354) seizure reduction. Lower baseline seizure frequency (<3 seizures/28 days) was significantly associated with a higher likelihood of achieving 100% seizure reduction (P=0.0002). None of the other baseline characteristics analyzed achieved significance.
Conclusions:
Results of this post-hoc analysis support the clinical intuition that patients with lower concomitant drug load and seizure frequency may be more likely to achieve seizure freedom with adjunctive cenobamate treatment. Adjunctive cenobamate resulted in high rates of seizure freedom in patients with uncontrolled epilepsy in the phase 3 study, particularly when compared to historical rates observed with other ASMs. See also abstract by Stern et al.