Abstract Details

Title Sudden Unexpected Death in Epilepsy During the Cenobamate Clinical Development Program

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P12 - Poster Session 12 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-012

Objective To assess all-cause mortality and sudden unexpected death in epilepsy (SUDEP) during the cenobamate clinical trial program.

Background The all-cause mortality rate in people with epilepsy is higher than in the general population for various reasons, including SUDEP. In a pooled analysis of 4 antiseizure medication (ASM) development programs involving 9144 adults and children with 13,617 person-years, all-cause mortality and SUDEP rates were 9.1 and 3.8, respectively, per 1000 person-years.

Design/Methods We analyzed deaths among adults with uncontrolled focal (focal to bilateral tonic-clonic [FBTC], focal impaired awareness, focal aware) or primary generalized tonic-clonic (PGTC) seizures who received ≥1 dose of adjunctive cenobamate in completed and ongoing phase 2 and 3 clinical studies. In patients with focal seizures from completed studies, median baseline seizure frequencies ranged from 2.8-11 seizures/28 days; median epilepsy duration ranged from 20-24 years. Total person-years included all days a patient received cenobamate during completed studies or up to a June 1, 2022, cutoff for ongoing studies. Deaths were evaluated by 2 epileptologists. All-cause mortality and SUDEP rates were expressed per 1000 person-years.

Results 2131 patients (n=2017 focal epilepsy; n=114 idiopathic generalized epilepsy) were exposed to cenobamate for 5693 person-years; ~60% of patients with focal seizures and all patients in the PGTC study had tonic-clonic seizures. Twenty-three deaths occurred (all in patients with focal epilepsy), for an all-cause mortality rate of 4 per 1000 person-years. Five cases of definite or probable SUDEP were identified for a rate of 0.88 per 1000 person-years. Of the 23 deaths, 21 patients (91%) had FBTC, and 4 of the 5 SUDEP patients had FBTC seizures. Duration of cenobamate exposure for patients with SUDEP ranged from 130-620 days.

Conclusions The all-cause mortality and SUDEP rates among patients with uncontrolled seizures enrolled in the cenobamate development program compare favorably to previously reported rates in other ASM development programs.

Authors/Disclosures
William E. Rosenfeld, MD, FAAN (Comprehensive Epilepsy Care Center for Children and Adults) PRESENTER	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 $100,000-$499,999 for serving on a Speakers Bureau for SK Life Science.
Louis Ferrari (SK Lifescience)	Louis Ferrari has received personal compensation for serving as an employee of SK Life science.
Marc Kamin, MD	Dr. Kamin has received personal compensation for serving as an employee of SK LIFE SCIENCE INC.
Michael R. Sperling, MD, FAAN (Thomas Jefferson University)	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 .

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