Abstract Details

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.