Lundbeck's Bexicaserin Shows Sustained Seizure Reduction in Rare Childhood Epilepsies After Two Years of Treatment
Key Insights
Lundbeck announced positive long-term data for bexicaserin showing sustained seizure reduction in patients with Developmental and Epileptic Encephalopathies (search) (DEEs (search)) for up to two years.
Patients experienced median reductions in countable motor seizures of 60.2% at 18 months and 53.7% at 24 months compared to baseline.
The investigational 5-HT2C (search) receptor superagonist demonstrated consistent efficacy across diverse DEE types with a favorable safety profile.
H. Lundbeck A/S announced compelling long-term efficacy data for bexicaserin (LP352), an investigational treatment for seizures associated with Developmental and Epileptic Encephalopathies (search) (DEEs (search)), at the 2025 American Epilepsy Society Congress in Atlanta. The data demonstrate that patients who achieved early seizure reduction continue to maintain this clinical benefit for up to two years of treatment.
Sustained Seizure Control Across DEE Subtypes
The long-term follow-up study tracked patients who completed the Phase 1b/2a PACIFIC trial, followed by a 12-month Open Label Extension (OLE), and continued treatment through Expanded Access. During the two-year follow-up period, patients receiving bexicaserin experienced a median reduction in countable motor seizures of 60.2% at approximately 18 months (n=30) and 53.7% at approximately 24 months (n=17), compared to the start of the PACIFIC trial.
Notably, these reductions were consistent across different DEE types and similar to the results observed in the original PACIFIC trial and OLE, indicating that patients of all DEE subtypes who experience an early, clinically meaningful response continue to maintain this response long-term.
Addressing Critical Unmet Medical Need
DEEs (search) represent a group of severe, rare epilepsies that begin in childhood and demand lifelong care. These heterogeneous epilepsy syndromes are characterized by refractory seizures, frequent epileptiform activity on electroencephalogram (EEG), and developmental stagnation or regression. According to the International League Against Epilepsy (ILAE), DEEs currently encompass more than 10 syndromes, including Early Infantile DEE (search) (EIDEE), Infantile Epileptic Spasms Syndrome (search) (IESS), Dravet Syndrome (search), and Lennox-Gastaut Syndrome (search).
Most DEE cases are resistant to conventional anti-seizure medications (ASMs), and there are currently no ASMs approved across all DEE subtypes, leaving many patients without suitable treatment options. The unpredictable nature of the seizures adds to the daily distress faced by families.
"The constant management of DEEs (search) place a heavy emotional and financial burden on families, underscoring the urgent need for better seizure control. We are increasingly hopeful that bexicaserin can address this need," said Johan Luthman, EVP and Head of Research and Development at Lundbeck. "The data so far show durable seizure reductions, an encouraging safety profile and minimal risk of drug-drug interactions, reinforcing bexicaserin's potential as a first-in-class therapy across a broad range of DEEs."
Novel Mechanism of Action and Safety Profile
Bexicaserin is an oral, centrally acting 5-hydroxytryptamine 2C (5-HT2C (search)) receptor superagonist with no engagement of the 5-HT2B and 5-HT2A receptor subtypes, potentially minimizing the risk of cardiovascular toxicity. No new safety concerns were observed during the two-year treatment phase, with a tolerability and safety profile similar to the PACIFIC trial and OLE.
The most common treatment-emergent adverse events (TEAEs) associated with bexicaserin in the PACIFIC trial were somnolence, decreased appetite, constipation, diarrhea, lethargy, tremor, urinary tract infection, fatigue, pyrexia, agitation, and hypertension.
Clinical Trial Design and Patient Population
The PACIFIC trial was a Phase 1b/2a randomized, double-blind, placebo-controlled clinical trial that assessed the safety, tolerability, efficacy, and pharmacokinetics of bexicaserin in 52 participants between the ages of 12 and 65 years old with any type of DEE at 34 sites across the United States and Australia. Participants were required to have at least four countable motor seizures during the 28-day baseline period while on a stable regimen of 1 to 4 concomitant antiseizure medications.
Following a 28-day baseline period, study participants initiated dose titration over 15 days and subsequently continued on the highest tolerated dose throughout a 60-day maintenance period. The OLE included patients with Dravet syndrome (search) (n=3), Lennox-Gastaut syndrome (search) (n=20) and DEE Other (n=18) who completed the PACIFIC trial (n=41).
Regulatory Recognition and Future Development
Bexicaserin has received significant regulatory recognition for its therapeutic potential. The FDA has granted Breakthrough Therapy designation for bexicaserin for the treatment of seizures associated with DEEs (search) for patients two years of age and older. The compound has also recently been granted Breakthrough Therapy Designation in China for the same indication.
The drug is currently being evaluated in a global Phase 3 clinical program called the DEEp Program. The full results of the PACIFIC trial were recently published in Epilepsia, a leading neurology journal, marking a significant milestone in advancing research within the field of DEEs (search).
With seven additional presentations at AES 2025, Lundbeck demonstrates the breadth of its research and development program and dedication to improving outcomes for children and families affected by rare epilepsies.