Predictors of Achievement of Response With Cenobamate: Post-hoc Subset Analysis From a Phase 3, Open-Label Safety Study (S44.006)

Abstract

<h3>Objective:</h3> 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. <h3>Background:</h3> The ability to predict a high likelihood of seizure freedom with cenobamate treatment could help with clinical antiseizure medication (ASM) selection. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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 (&lt;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. <h3>Conclusions:</h3> 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. <b>Disclosure:</b> The institution of Dr. Wechsler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Otsuka. The institution of Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. The institution of Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for SK Life Science. The institution of Dr. Wechsler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Aquestive. The institution of Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Engage. The institution of Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Greenwich. The institution of Dr. Wechsler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerevel. The institution of Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eisai. The institution of Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sunovion. The institution of Dr. Wechsler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eliem. The institution of Dr. Wechsler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. The institution of Dr. Wechsler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epalex. The institution of Dr. Wechsler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Engrail. The institution of Dr. Wechsler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurona. Dr. Wechsler has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Neurelis. Dr. Wechsler has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Sunovion. Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for UCB. Dr. Wechsler has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Greenwich. Dr. Wechsler has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Eisai. Dr. Wechsler has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Aquestive. Dr. Wechsler has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for SK Life Science. Dr. Wechsler has a non-compensated relationship as a Board President with Epilepsy Foundation of Idaho that is relevant to AAN interests or activities. Dr. Vossler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex Pharmaceuticals. Dr. Vossler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Longboard Pharmaceuticals. The institution of Dr. Vossler has received research support from SK Life Science. The institution of Dr. Vossler has received research support from Xenon Pharmaceuticals. The institution of Dr. Vossler has received research support from Longboard Pharmaceuticals. The institution of Dr. Kerr has received research support from NIH. Dr. Kerr has received publishing royalties from a publication relating to health care. Mr. Stern has received personal compensation for serving as an employee of SK Life Science. Mr. Wade has nothing to disclose. The institution of Dr. Rosenfeld has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for SK Life Science. Dr. Rosenfeld has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for SK Life Science. The institution of Dr. Rosenfeld has received research support from SK Life Science. The institution of Dr. Rosenfeld has received research support from UCB Pharma.