Abstract Details

Title Efficacy and Safety of Adjunctive Cenobamate for the Treatment of Primary Generalized Tonic-clonic Seizures in Adults and Adolescents

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P3 - Poster Session 3 (5:00 PM-6:00 PM)

Poster/Presentation
Number 10-003

Objective To assess the efficacy and safety of adjunctive cenobamate for the treatment of primary generalized tonic-clonic (PGTC) seizures in patients ≥12 years old.

Background Cenobamate is an antiseizure medication (ASM) indicated for treating focal seizures in adults.

Design/Methods

This phase 3, multicenter, double-blind trial (YKP3089C025; NCT03678753) randomized patients with PGTC seizures 1:1 to cenobamate 200 mg/day or matching placebo administered as an oral tablet in adults (≥18 years) or weight-based equivalent pediatric oral suspension in adolescents (≥12 to <18 years). Patients must have had ≥5 PGTC seizures during the 12-week baseline period (≥1.67 seizures/28 days) despite treatment with 1-3 ASMs. Cenobamate dosing started at 12.5 mg/day (or weight-based equivalent) and was titrated to 150 mg/day (or weight-based equivalent) over 10 weeks. Cenobamate was dosed at 200 mg/day (or weight-based equivalent; minimum 150 mg/day) during the 12-week maintenance phase. Primary efficacy outcomes were median percent change from baseline in 28-day PGTC seizure frequency during the double-blind period and ≥50% responder rates during the maintenance phase. Safety was also assessed.

Results Among 169 patients randomized (n=135 adults, n=34 adolescents), 168 (placebo, n=83; cenobamate, n=85) were included in the analysis. Median percent reduction from baseline in seizure frequency/28 days during the double-blind period was 71.9% for cenobamate (vs 39.6% placebo, P=0.003). Among the 161 patients (placebo, n=78; cenobamate, n=83) analyzed during the maintenance-phase, the ≥50% responder rate was 71.1% for cenobamate (vs 51.3% placebo, P=0.01); 43.4% of cenobamate-treated patients were seizure-free (vs 20.5% placebo, P=0.002). Treatment-emergent adverse events occurred in 53.0% (44/83) of placebo-treated patients and 60.0% (51/85) of cenobamate-treated patients (most commonly somnolence [16.5%] and fatigue [10.6%] for cenobamate). No treatment-related serious adverse events, deaths, or cases of drug reaction with eosinophilia and systemic symptoms (DRESS) were reported.

Conclusions Adjunctive cenobamate 200 mg/day demonstrated efficacy and safety in treating PGTC seizures in patients ≥12 years old.

Authors/Disclosures
Pavel Klein, MD, FAAN (Mid-atlantic Epilepsy and Sleep Center) PRESENTER	The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Aquestive. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurelis. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB Pharma. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for SK Life Sience. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alliance. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvelle Therapeutics. Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Aquestive. Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Eisai. Dr. Klein has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for UCB Pharma. Dr. Klein has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for SK Life Sciences. Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sunovion. Dr. Klein has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for PrevEp. Dr. Klein has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Fenwick . Dr. Klein has received research support from DOD/CURE.
Evelyn K. Shih, MD, PhD (Neurelis, Inc.)	Dr. Shih has received personal compensation for serving as an employee of Neurelis, Inc. Dr. Shih has received personal compensation for serving as an employee of SK Life Science, Inc.
Michal Bar, MD, PhD	Prof. Bar has nothing to disclose.
Mark K. Farkas, MD, PhD	Dr. Farkas has nothing to disclose.
David G. Vossler, MD, FAAN (David G. Vossler MD FAAN FAES FACNS)	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. 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 Xenon Pharmaceuticals. Dr. Vossler has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for 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. Dr. Vossler has received publishing royalties from a publication relating to health care.
Sunita N. Misra, MD (SK Life Science)	Dr. Misra has received personal compensation for serving as an employee of SK Life Science, Inc. An immediate family member of Dr. Misra has received personal compensation for serving as an employee of Neurocrine Biosciences.

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