Bexicaserin, an investigational drug developed by Longboard Pharmaceuticals (now Lundbeck), has demonstrated significant and sustained reductions in seizure frequency among patients with developmental and epileptic encephalopathies (DEEs). Interim results from the Phase 1b/2a PACIFIC open-label extension (OLE) study showed that patients who switched from placebo to bexicaserin experienced notable improvements, reinforcing the drug's potential as a treatment for a range of DEEs.
The PACIFIC OLE study, which included 41 patients across 34 sites, involved a 15-day flexible titration period followed by up to one year of maintenance treatment. The analysis focused on nine patients previously randomized to placebo who then switched to bexicaserin for six months. Led by Dr. Ngoc Minh D. Le, the study revealed a -57.3% reduction in countable motor seizures (CMS) and a -61.2% reduction in total seizures in this group. More than half (55.6%) of these participants achieved at least a 50% reduction in CMS frequency.
Consistent Efficacy Across DEE Subgroups
The study population included patients with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and other DEEs. Bexicaserin maintained its safety profile throughout the OLE, with no new serious adverse events reported. Investigators noted that the consistent seizure reductions across DEE subgroups highlight the therapeutic's potential for broader application.
Mechanism of Action and Prior Trial Data
Bexicaserin is a selective 5-HT2c receptor superagonist believed to modulate GABAergic neurotransmission, suppressing central hyperexcitability. In the original PACIFIC trial, participants aged 12-65 years with DEEs were evaluated for safety, tolerability, efficacy, and pharmacokinetics of oral bexicaserin at different doses versus placebo. Results from the initial trial showed a median decrease of 53.3% in CMS for those on bexicaserin versus a 20.8% decrease for those on placebo.
Phase 3 Development and Future Studies
Longboard initiated a global Phase 3 study called DEEp SEA to assess bexicaserin's therapeutic potential in patients with DS aged two years and older. This trial aims to include approximately 160 participants who will undergo a screening period, dose titration phase, and maintenance period. The DEEp SEA study is part of a broader DEEp program involving around 480 participants with various DEEs across 80 sites globally. Another Phase III clinical trial, DEEp OCEAN, will monitor countable motor seizures in nearly 320 participants aged between two and 65 years.
Industry Perspective
"We are very pleased to observe a longer-term sustainable response, along with a favorable safety and tolerability profile over a 12-month period. These results further reinforce our confidence in bexicaserin’s unique and potentially best-in-class profile," said Johan Luthman, EVP and Head of Research & Development at Lundbeck.
