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Abstract Details

Efficacy and Safety of Bexicaserin (LP352) in Adolescent and Adult Patients with Developmental and Epileptic Encephalopathies (DEEs): Results of the Phase 1b/2a PACIFIC Study
Epilepsy/Clinical Neurophysiology (EEG)
ES1 - Emerging Science 1 (11:27 AM-11:33 AM)
003

DEEs are the most severe group of epilepsies characterized by drug-resistant seizures, epileptiform abnormalities, and developmental slowing or regression. DEE trials have focused on patients with specific epilepsy syndromes such as Dravet syndrome (DS), Tuberous Sclerosis Complex, and Lennox-Gastaut Syndrome (LGS), the latter has etiological heterogeneity. Here, we present a novel Phase 1b/2a study of patients with DEEs treated with bexicaserin, a potent and highly selective 5-HT2C receptor superagonist.

To assess safety, tolerability, pharmacokinetics, and efficacy of bexicaserin (LP352) for treatment of seizures in developmental and epileptic encephalopathies (DEEs).

The PACIFIC study investigated the safety, tolerability, pharmacokinetics, and efficacy of bexicaserin for seizure treatment in patients aged 12-65 years with DEEs (DS, LGS, and DEE Other). Patients were randomized (4:1) to bexicaserin or placebo and underwent a 15-day flexible titration period (maximum dose of 12 mg TID, based on tolerability), followed by 60 days of maintenance, and a 5- to 15-day taper. Key inclusion criteria included ≥4 countable motor seizures during 28-day screening and ≤4 concomitant antiseizure medications. Key exclusion criteria included use of fenfluramine. No echocardiogram monitoring was performed.

52 patients (43 bexicaserin, 9 placebo) were enrolled (29 LGS, 4 DS, and 19 DEE Other) across 34 sites. 35 patients took bexicaserin in the full analysis set, with 30 (85.7%) achieving maximum dosing. Most common adverse events were somnolence, decreased appetite, constipation, and diarrhea. Median countable motor seizure reduction with bexicaserin was 59.8% versus 17.4% with placebo. Median motor seizure reduction in DS was 74.6% (no placebo comparator), LGS 50.8% (placebo: 17.4%), and DEE Other 65.5% (placebo: 32.2%).

Bexicaserin exhibited a favorable safety and tolerability profile in this study. Efficacy as assessed by seizure reduction was similar in all subgroups, including LGS and DEE Other, which are highly etiologically heterogeneous disorders.

Authors/Disclosures

PRESENTER
No disclosure on file
Chadwick Orevillo Mr. Orevillo has received personal compensation for serving as an employee of Longboard Pharmaceuticals, Inc..
Dennis Dlugos Dr. Dlugos has received research support from NIH. The institution of Dr. Dlugos has received research support from The Epilepsy Study Consortium.
Ingrid Scheffer (Melbourne Brain Centre) Dr. Scheffer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biohaven Pharmaceuticals, Inc. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerecin Inc. The institution of Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epilepsy Consortium. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Longboard Pharmaceuticals . Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bellberry Ltd. The institution of Dr. Scheffer has received research support from National Health and Medical Research Council, Australia. The institution of Dr. Scheffer has received research support from National Health and Medical Research Council, Australia. The institution of Dr. Scheffer has received research support from National Health and Medical Research Council, Australia. The institution of Dr. Scheffer has received research support from Medical Research Future Fund, Australia. The institution of Dr. Scheffer has received research support from Medical Research Future Fund, Australia. The institution of Dr. Scheffer has received research support from Medical Research Future Fund, Australia. The institution of Dr. Scheffer has received research support from Medical Research Future Fund, Australia. The institution of Dr. Scheffer has received research support from Medical Research Future Fund, Australia. The institution of Dr. Scheffer has received research support from Shenzhen Sanming Development Grant . The institution of Dr. Scheffer has received research support from Einstein Visiting Fellowship. Dr. Scheffer has received intellectual property interests from a discovery or technology relating to health care. Dr. Scheffer has received intellectual property interests from a discovery or technology relating to health care. Dr. Scheffer has received intellectual property interests from a discovery or technology relating to health care. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Speaker honoraria with Akumentis. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Travel/Conference/Speaker honoraria with Biocodex. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Travel/Conference/Speaker honoraria with BioMarin. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Speaker honoraria with Chiesi. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Travel/Conference/Speaker honoraria with Eisai. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Travel/Conference with Encoded Therapeutics. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Speaker honoraria with Liva Nova. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Speaker honoraria with Nutricia. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Travel/Conference/Speaker honoraria with Stoke Therapeutics. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Travel/Conference/Speaker honoraria with UCB. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Speaker honoraria with Zuellig Pharma Inc.. Dr. Scheffer has a non-compensated relationship as a Trial Investigator with Anavex Life Sciences that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Cerebral Therapeutics that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Cerecin that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Cereval Therapeutics that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Eisai that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Scientific Advisory Board, Trial investigator with Encoded Therapeutics that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with EpiMinder Inc that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with ES-Therapeutics that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Knopp Biosciences that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Marinus Pharmaceuticals that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Neurocrine BioSciences that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Ovid Therapeutics that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with SK Life Science that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator, Scientific Advisory Board with Takeda Pharmaceuticals that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Xenon Pharmaceuticals that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Zogenix that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Journal Editorial Board with Neurology that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Journal Editorial Board with Epilepsy Currents that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Journal Editorial Board with Epileptic Disorders that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Journal Editorial Board with The Lancet Neurology that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Journal Editorial Board with Progress in Epileptic Disorders series that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Director with Australian Academy of Health and Medical Sciences that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Director with Royal Society (Australia). that is relevant to AAN interests or activities.