<h3>Objective:</h3> 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. <h3>Background:</h3> Cenobamate is an antiseizure medication (ASM) approved in the US and EU for the treatment of focal seizures. <h3>Design/Methods:</h3> 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). <h3>Results:</h3> 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. <h3>Conclusions:</h3> 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. <b>Disclosure:</b> Mr. Stern has received personal compensation for serving as an employee of 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 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. 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. Wade has nothing to disclose. 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. 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.