Abstract Details

Title Safety of Cenobamate (YKP3089) as Adjunctive Treatment for Uncontrolled Focal Seizures in a Large, Multicenter, Open-Label Study

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-019

Objective To assess whether a slower titration rate than that utilized in early studies would reduce the incidence of drug reaction with eosinophilia and systemic symptoms (DRESS) in patients taking the investigational antiepileptic drug (AED) cenobamate.

Background Two adequate and well-controlled studies demonstrated that adjunctive cenobamate decreases focal seizure frequency. During early clinical development, among the first 953 adults exposed to cenobamate, three confirmed cases of DRESS occurred.

Design/Methods This ongoing multicenter, open-label study enrolled epilepsy patients 18-70 years old with uncontrolled focal seizures taking stable doses of 1-3 AEDs. Increasing daily doses of cenobamate were administered (12.5, 25, 50, 100, 150, and 200 mg/day) at 2-week intervals. Further increases to 400 mg/day by 50-mg/day increments every other week were allowed. Patient visits occurred every 2 weeks for 16 weeks and then every 1-3 months. Serious adverse events (SAEs) were reported according to local regulatory requirements. All hypersensitivity reactions were reviewed monthly to screen for DRESS. Although the study is ongoing, new enrollment ended when at least 1000 patients had been exposed to cenobamate for ≥6 months.

Results At data cut-off, 1348 patients had been enrolled, 1037 were exposed to cenobamate for ≥196 days, and 273 discontinued therapy. Four deaths were reported: sudden death with no autopsy, traumatic intracerebral hemorrhage after a fall, fatal injuries after being struck by a car, and respiratory failure in a patient with Angelman syndrome. Overall, 114 patients (8.5%) had an SAE, most commonly hospitalization for seizure. The most common adverse events were somnolence, dizziness, and fatigue. No cases of DRESS were identified.

Conclusions Results to date from this ongoing safety study of cenobamate found no cases of DRESS. Adverse events were most commonly central nervous system-related. Reducing the starting dose of cenobamate and slowing the titration rate to 2-week intervals appears to mitigate the risk of DRESS.

Authors/Disclosures
Michael R. Sperling, MD, FAAN (Thomas Jefferson University) PRESENTER	Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. The institution of Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Pharma. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medscape. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for International Medical Press. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Projects for Knowledge. The institution of Dr. Sperling has received research support from SK Life Science. The institution of Dr. Sperling has received research support from UCB Pharma . The institution of Dr. Sperling has received research support from Takeda. The institution of Dr. Sperling has received research support from Neurelis. The institution of Dr. Sperling has received research support from Engage Therapeutics . The institution of Dr. Sperling has received research support from Medtronic. The institution of Dr. Sperling has received research support from Cavion. The institution of Dr. Sperling has received research support from Xenon Pharma. The institution of Dr. Sperling has received research support from Cerevel. The institution of Dr. Sperling has received research support from National Institutes of Health . The institution of Dr. Sperling has received research support from DARPA. Dr. Sperling has received publishing royalties from a publication relating to health care. Dr. Sperling has received publishing royalties from a publication relating to health care. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Vice President with Epilepsy Consortium .
Pavel Klein, MD, FAAN (Mid-atlantic Epilepsy and Sleep Center)	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.
Marc Kamin, MD	Dr. Kamin has received personal compensation for serving as an employee of SK LIFE SCIENCE INC.

��ɫ��

��ɫ��