Bexicaserin Demonstrates Similar Reduction of Countable Motor Seizures in Adolescents and Adults with Developmental and Epileptic Encephalopathies: Analysis of the Phase 1b/2a PACIFIC Study
Abstract number :
3.399
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2024
Submission ID :
400
Source :
www.aesnet.org
Presentation date :
12/9/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Nilika Singhal, MD – University of California, San Francisco
David G Vossler, MD – University of Washington School of Medicine
Dewey McLin, PhD – Longboard Pharmaceuticals, Inc.
Ngoc Minh Le, MD – Longboard Pharmaceuticals, Inc.
Morgan Weberg, BS – Longboard Pharmaceuticals, Inc.
Chad Orevillo, MPH – Longboard Pharmaceuticals, Inc.
Randall Kaye, MD – Longboard Pharmaceuticals, Inc.
Rationale: The PACIFIC study (LP352-201, NCT05364021), which enrolled participants 12-65 years of age, showed meaningful reduction in countable motor seizures (CMS; 59.8% in bexicaserin versus 17.4% in placebo groups), and a favorable safety profile. Patient age may affect the efficacy and safety of some anti-seizure medications (ASMs), due to possible factors such as changes in neurological development, seizure type/presentation, and pharmacokinetics (e.g., French JA and Staley BA, Epilepsy Currents, 2012) over time. To better understand the efficacy of bexicaserin as it relates to age and assess whether there are identifiable age-related differences in response prior to proceeding to Phase 3, we performed a post-hoc analysis of the Phase 1b/2a PACIFIC data for adolescent and adult subgroups.
Methods: Patients with developmental and epileptic encephalopathies (DEEs; Dravet syndrome [DS], Lennox-Gastaut syndrome [LGS], or DEE Other) were eligible to enroll in the PACIFIC study if they were 12-65 years of age, experienced an average of ≥4 CMS per 28-days during the 12 weeks before screening, and were taking 1-4 concomitant ASMs. Participants were randomly assigned (4:1) to receive bexicaserin (targeted highest dose of 12 mg three times daily [TID], based on tolerability) or placebo, in addition to their concomitant ASM regimen. Following a 15-day titration period, each participant’s maximum tolerated dose (6, 9, or 12 mg TID) was maintained for 60 days, and then tapered off over 5 to 15 days.
Results: Fifty-two participants were enrolled (4 DS, 29 LGS, and 19 DEE Other) and randomly assigned to the bexicaserin (n=43) or placebo (n=9) groups. Of these, 35/43 and 9/9, respectively, entered the maintenance period. By chance, no adolescents were assigned to the placebo group. Among participants randomized to receive bexicaserin, 10 were 12-17 years of age and 25 were 18-65 years of age. The median percent reduction in observable CMS was 64.4% in participants 12-17 years of age and 59.8% among participants ≥18 years of age taking bexicaserin.
Conclusions: In this post-hoc analysis, adolescent and adult participants with DEEs achieved similar reductions of CMS frequency during treatment with bexicaserin compared to baseline. Both age groups demonstrated substantial reductions of CMS frequency that were comparable to previously reported aggregate data. These results provide support for the inclusion of younger participants in future Phase 3 studies of bexicaserin for the treatment of seizures in DEEs, which typically emerge during the first few years of life.
Funding: This study was sponsored by Longboard Pharmaceuticals, Inc.
Anti-seizure Medications