Authors :
Presenting Author: Jonathan Williams, PharmD – Longboard Pharmaceuticals, Inc.
Nuggehally Srinivas, PhD – Longboard Pharmaceuticals, Inc.
Rosa Chan, PhD – Longboard Pharmaceuticals, Inc.
Dewey McLin, PhD – Longboard Pharmaceuticals, Inc.
Chad Orevillo, MPH – Longboard Pharmaceuticals, Inc.
Ngoc Minh Le, MD – Longboard Pharmaceuticals, Inc.
Randall Kaye, MD – Longboard Pharmaceuticals, Inc.
Rationale: Patients with developmental and epileptic encephalopathies (DEEs) encompass the most severe group of epilepsies and are characterized by drug-resistant seizures, epileptiform abnormalities, and developmental slowing or regression. Complex polypharmacy is standard in patients with DEEs. Bexicaserin is an oral, centrally acting, highly selective 5-HT
2C superagonist in development for treatment of patients with DEEs. Given the extent of polypharmacy in this population, it is anticipated bexicaserin will frequently be used in conjunction with other antiseizure medications (ASMs). Therefore, avoidance of drug-drug interactions (DDIs) in this population is particularly desirable, and it is important to thoughtfully evaluate and characterize bexicaserin’s DDI potential. Here, the effect of bexicaserin as a potential perpetrator of DDIs with co-administered ASMs is evaluated.
Methods: PACIFIC (LP352-201, NCT05364021) was a Phase 1b/2a study which enrolled patients taking stable doses of 1 – 4 concomitant ASMs. Trough blood samples were collected at ‘Baseline’ and ‘post-Baseline’ at Days 1, 6, 11, 15, and 30 (all ±3 days except for Day 1). The samples were analyzed at a reference laboratory for concentrations of each concomitant ASM and/or its metabolite, as applicable. Dose-normalized trough ASM concentrations at Baseline were compared with dose-normalized trough ASM concentrations post-Baseline for the respective ASMs at individual visits. Additionally, post-Baseline dose-normalized trough ASM concentrations from all visits were pooled by ASM and compared to Baseline (‘pre-treatment’ dose-normalized trough ASM concentrations). Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were calculated. Results were summarized in a Forest Plot. Box plots were generated to longitudinally visualize dose-normalized trough ASM concentrations at all visits.
Results:
Blood samples were evaluated from patients who contributed at least 1 post-Baseline ASM concentration. The dose-normalized trough ASM concentrations of at least fourteen ASMs were comparable between pre- versus post-Baseline in patients with DEEs from the PACIFIC study. ASM concentrations were stable across visits; GMRs for trough concentrations, comparing pre- versus post-Baseline, approximated 1 for all ASMs. Most 90% CIs included 1, with almost equal spread across the line of unity.
Conclusions: The data demonstrated no apparent clinically meaningful effect of bexciaserin on the pharmacokinetics of co-administered ASMs in this study; concentrations remained stable across all visits. Drug-drug interaction (perpetrator) potential was low for bexicaserin when co-administered with ASMs commonly used by PACIFIC study participants. In the treatment of patients with DEEs in the PACIFIC study, bexicaserin appeared to be safely added to patients’ ASM regimens, regardless of the concomitant ASM(s) or dose.
Funding: This study was sponsored by Longboard Pharmaceuticals, Inc.