Authors :
Presenting Author: Caitlin Sylvia, BS – H. Lundbeck A/S, Copenhagen, Denmark
Shikha Polega, PharmD – H. Lundbeck A/S, Copenhagen, Denmark
Nadine Knowles, MS – H. Lundbeck A/S, Copenhagen, Denmark
Randall Kaye, MD – Longboard Pharmaceuticals (now a part of H. Lundbeck A/S), La Jolla, CA, USA
Henrik Loft, MSc, PhD – H. Lundbeck A/S, Copenhagen, Denmark
Tolga Uz, PhD – H. Lundbeck A/S, Copenhagen, Denmark
Rationale:
Developmental and epileptic encephalopathies (DEEs) are the most severe epilepsies, characterized by treatment-resistant seizures, frequent epileptiform activity, and developmental slowing or regression.1 The clinical trial program for bexicaserin—an investigational, highly selective superagonist of the 5-hydroxytryptamine type 2C (5-HT2C) receptor—includes the first regulatory-endorsed single trial inclusive of all DEEs. Bexicaserin was well tolerated in the Phase 1b/2a PACIFIC trial (RCT) and 12-month open-label extension (OLE) with a favorable safety profile and similar reductions in countable motor seizures in Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and other DEEs (DEE Other). The Expanded Access Program (EAP) provides further access to bexicaserin in this underserved population. Here, we report an interim analysis of the EAP in the group of participants who rolled over from the OLE and have received up to 2 years of bexicaserin treatment (OLE + EAP).
Methods:
This analysis included participants who completed the Phase 1b/2a PACIFIC RCT and OLE and enrolled in the EAP. Data reflect staggered entry into the EAP and/or staggered seizure diary data entry.
Results:
Of 38 participants who completed the 12-month Phase 1b/2a OLE, 36 enrolled immediately in the EAP and continued their maintenance dosing regimen. At approximately 18 months treatment (OLE + EAP), one participant was lost to follow-up, and one participant was reported as deceased unrelated to study drug; the remaining 34 EAP participants on bexicaserin received approximately 24 months of treatment. Compared with the safety profile during the OLE, no new safety signals were observed. Relative to RCT baseline, the median percentage change in countable motor seizure frequency was -60.2% (n=30) at ~18 months, and -53.7% (n=17) at ~24 months. Seizure reductions were seen across participant subgroups at ~18 months (DS, -73.0% [n=3]; LGS, -51.2% [n=12]; DEE Other, -61.5% [n=15]) and ~24 months (DS, -100% [n=1]; LGS, -37.1% [n=6]; DEE Other, -73% [n=10]) of treatment.
Conclusions:
Bexicaserin continues to exhibit a favorable safety and tolerability profile in participants with any type of DEE for up to 2 years of treatment. Comparable reductions in countable motor seizures between the RCT, OLE, and EAP reinforce the durability and consistency of bexicaserin efficacy across DEEs, further validating its progression into Phase 3 trials.
1. Scheffer I, et al. Epilepsia. 2025;66:1014-1023.
Funding:
This study was sponsored by Longboard Pharmaceuticals, Inc, now a part of H. Lundbeck A/S.