Primary Results of the 12-month Open-label Extension of the Phase 1b/2a PACIFIC Trial of Bexicaserin for the Treatment of Seizures in Participants with Developmental and Epileptic Encephalopathies Demonstrates Long-term Safety, Tolerability, and Efficacy
Dennis J. Dlugos1, Ingrid E. Scheffer2, Jacqueline A. French3, David G. Vossler4, Tolga Uz5, Nadine Knowles5, Randall Kaye6, Shikha Polega5
1Children’s Hospital of Philadelphia, Philadelphia, PA, USA, 2Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Department of Paediatrics, Royal Children's Hospital, The University of Melbourne, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health and Murdoch Children's Research Institute, Parkville, Victoria, Australia, 3New York University Grossman School of Medicine, New York, NY, USA, 4University of Washington School of Medicine, Seattle, WA, USA, 5H. Lundbeck A/S, Copenhagen, Denmark, 6Longboard Pharmaceuticals (now a part of H. Lundbeck A/S), La Jolla, CA, USA
Objective:
The study objective was to evaluate the safety, tolerability, and efficacy of bexicaserin in participants with developmental and epileptic encephalopathies (DEEs) in a clinical trial open-label extension (OLE).
Background:
DEEs, associated with frequent epileptiform activity, treatment-resistant seizures, and developmental slowing or regression, are the most severe group of epilepsies. Bexicaserin, a highly selective 5-hydroxytryptamine type 2C (5-HT2C) receptor superagonist, is under development for treatment of seizures in patients with DEEs. In the randomized, double-blind Phase 1b/2a PACIFIC trial (RCT), bexicaserin was well tolerated and reduced countable motor seizure frequency to a similar extent across Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and other DEEs (DEE Other).
Design/Methods:
Upon completion of the RCT, participants were able to enroll in the OLE, which continued to investigate safety, tolerability, and efficacy for 12 additional months. Participants aged 12-65 years with DS, LGS, or DEE Other underwent an open-label treatment period inclusive of a 15-day flexible titration period (maximum 12 mg TID, based on tolerability), followed by a maintenance period. Changes from RCT baseline through OLE Month 12 were evaluated.
Results:
All participants who completed the RCT (N=41: 32 bexicaserin, 9 placebo; 3 DS, 20 LGS,18 DEE Other) chose to enroll in the OLE, and 92.7% (n=38) completed the 12-month period. Adverse events were consistent with those observed in the RCT, and no new safety signals were reported. Countable motor seizure frequency was reduced by a median of 59.3%, and 55% of participants experienced a ≥50% reduction from RCT baseline.
Conclusions:
Bexicaserin was well tolerated over the 12-month OLE, underscored by high enrollment (100%) and completion (92.7%) rates. Efficacy was durable and consistent across a variety of DEEs; comparable seizure reductions in both RCT and OLE were observed. These results further support the progression of bexicaserin into Phase 3 clinical development.
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