Abstract Details

Title Long-term Efficacy and Safety of Adjunctive Cenobamate in Patients With Uncontrolled Focal Seizures: Open-label Extension of a Randomized Clinical Study

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S59 - Epilepsy/Clinical Neurophysiology (EEG) 4 (2:36 PM-2:48 PM)

Poster/Presentation
Number 009

Objective To report long-term outcomes from the ongoing open-label extension (OLE) of the YKP3089C017 (C017) study.

Background In a pivotal study (C017), patients with drug-resistant focal epilepsy treated adjunctively with cenobamate achieved significantly greater reductions in median seizure frequency/month than placebo. Patients completing the double-blind (DB) period were eligible to continue in an OLE.

Design/Methods 437 adults with uncontrolled focal seizures and ≥8 focal seizures during an 8-week baseline period despite treatment with stable doses of 1-3 antiepileptic drugs were randomized 1:1:1:1 to placebo or cenobamate 100, 200, or 400mg once daily. There was a 6-week titration phase and 12-week maintenance phase. 360 patients completed the DB study. Patients entering the OLE underwent a 2-week blinded conversion to a target dose of cenobamate 300mg/day (max dose 400mg/day).

Results 98.6% of patients who completed the DB period entered the OLE. As of April 2018, 64.8% of patients were continuing in the OLE; 125 patients discontinued due to: lack of efficacy (15.5%), adverse events (6.8%), withdrawal by patient (6.5%), and other reasons (6.5%). Median duration of cenobamate exposure was 40.1 months; 69.6% (n=247) were treated for ≥24 months. Median modal daily cenobamate dose was 300mg. TEAEs occurred in 87.6% of patients during the OLE. TEAEs reported in ≥10% of patients were dizziness, somnolence, headache, diplopia, fatigue, and gait disturbance. Serious TEAEs occurred in 18.3% of patients. TEAEs leading to discontinuation occurred in 7.9% of patients. In the OLE intent-to-treat population (N=354), the median percent seizure frequency reduction during the first 6 months of treatment was 65.4% (n=354). At 25-30 months, seizure frequency reductions increased to a median 76.0% (n=223), with 20.2% of evaluable patients seizure-free.

Conclusions Reductions in seizure frequency were sustained during 30 months of cenobamate treatment. Cenobamate was generally well-tolerated long-term, with 69.6% of patients continuing treatment past 24 months.

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.
Gregory Krauss, MD (Johns Hopkins University)	Dr. Krauss has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvelle. Dr. Krauss has received stock or an ownership interest from EpiWatch.
Sami M. Aboumatar, MD (Austin Epilepsy Care Center)	Dr. Aboumatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Aboumatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SK Life Science, Inc.. Dr. Aboumatar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Aboumatar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sunovion.
Marc Kamin, MD	Dr. Kamin has received personal compensation for serving as an employee of SK LIFE SCIENCE INC.

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