Lundbeck A/S showcased data on bexicaserin, a novel investigational treatment for seizures associated with Developmental and Epileptic Encephalopathies (DEEs), at the American Epilepsy Society (AES) Annual Meeting in Los Angeles. The presentations highlighted bexicaserin's potential to address unmet needs in severe epilepsies, supported by its Breakthrough Therapy Designation (BTD) for DEEs from the FDA.
Bexicaserin's Clinical and Preclinical Profile
Bexicaserin (LP352) is an oral, centrally acting 5-hydroxytryptamine 2C (5-HT2C) receptor superagonist, exhibiting high selectivity and specificity with minimal impact on 5-HT2B and 5-HT2A receptor subtypes. The drug is currently under evaluation in the global Phase III DEEp Program. The FDA has also granted Orphan Drug Designation and Rare Pediatric Disease Designation for bexicaserin in Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS).
Data Presentations at AES
Several poster presentations at the AES Annual Meeting covered various aspects of bexicaserin's profile:
- PACIFIC Study Open-Label Extension (OLE): Interim results from the Phase 1b/2a PACIFIC study OLE assessed the safety, tolerability, and efficacy of bexicaserin in participants with DEEs (Poster 1.509).
- Efficacy Analyses of the PACIFIC Study: Additional analyses of the PACIFIC Study focused on responder rates, number needed to treat, and seizure-free days in participants with DEEs (Poster 1.402).
- SUDEP Mouse Model: Preclinical data demonstrated that bexicaserin reduces seizures and respiratory arrest in a mouse model of Sudden Unexpected Death in Epilepsy (SUDEP) (Poster 1.505).
- Receptor Selectivity: Bexicaserin exhibits high selectivity and specificity for the 5-HT2C receptor, with low potential for off-target activity (Poster 1.506).
- Caregiver Sleep Disruption: Preliminary results were presented from a controlled study of sleep disruption in caregivers of individuals with Lennox-Gastaut Syndrome (LGS) (Poster 1.531).
- Adolescent and Adult Motor Seizure Reduction: Analysis of the Phase 1b/2a PACIFIC Study showed similar reduction of countable motor seizures in adolescents and adults with DEEs (Poster 3.399).
- Drug-Drug Interaction Potential: Bexicaserin has negligible drug-drug interaction potential with frequently used antiseizure medications, as shown in a Phase 1b/2a study in participants with DEEs (Poster 3.400).
- Drug-Drug Interaction Assessment: A cocktail approach was used to assess the drug-drug interaction potential of bexicaserin as a perpetrator on the pharmacokinetics of substrates for renal, hepatic, efflux transporters, and CYP/UGT enzymes (Poster 3.401).
Commitment to Rare Epilepsy
Johan Luthman, EVP and Head of Research & Development at Lundbeck, stated that bexicaserin's profile addresses a significant unmet need in severe epilepsies where few treatments exist. The AES Annual Meeting provided an opportunity to engage with key opinion leaders and advocacy groups to discuss bexicaserin’s potential.
