H. Lundbeck A/S announced it will present comprehensive long-term efficacy data for bexicaserin at the 36th International Epilepsy Congress in Lisbon, demonstrating sustained seizure reduction in patients with developmental and epileptic encephalopathies (DEEs), the most severe form of rare epilepsies.
Extension Study Confirms Durable Efficacy
The complete results from the open-label extension (OLE) of the Phase 1b/2a PACIFIC trial will be presented for the first time, showing bexicaserin maintained its therapeutic effect over 52 weeks of treatment. During the extension study, patients experienced a median reduction of 59.3% in countable motor seizure frequency, with 55% of participants achieving sustained reductions of ≥50% compared to baseline before the PACIFIC trial.
"I am encouraged by the 100% enrollment of eligible participants and the high completion rate of over 90% in the open-label extension study. Such high retention underscores the tolerability as well as the duration of effect of bexicaserin across developmental and epileptic encephalopathies," said Ingrid E. Scheffer, lead investigator and Laureate Professor of Pediatric Neurology at The University of Melbourne and Austin Health.
The extension study included 41 patients who completed the original PACIFIC trial, comprising patients with Dravet syndrome (n=3), Lennox-Gastaut syndrome (n=20), and other DEEs (n=18). Bexicaserin was well tolerated throughout the 52-week period, with no new safety signals observed.
Breakthrough Therapy Advances to Phase 3
Bexicaserin has received FDA Breakthrough Therapy designation for treating seizures associated with DEEs in patients two years of age and older. The drug is an oral, centrally acting 5-hydroxytryptamine 2C (5-HT2C) receptor superagonist with selective engagement that potentially minimizes cardiovascular toxicity risks associated with nonselective serotonergic agents.
"As we are now in phase 3 trials with bexicaserin, we are optimistic about its potential. The clinical data so far suggests broad and durable anti-seizure activity across DEEs, and new preclinical data suggests modulation of the risk of sudden unexpected death in epilepsy (SUDEP)," said Johan Luthman, EVP and Head of Research and Development at Lundbeck.
The company has initiated its global Phase 3 program called DEEp, with two active trials. The DEEpSEA trial is recruiting participants with Dravet syndrome, while the DEEpOCEAN trial is enrolling individuals with various DEEs, including Lennox-Gastaut syndrome. Both randomized, double-blind, placebo-controlled trials are open for enrollment across North America, Europe, Asia, Australia, and Latin America.
Preclinical Data Addresses SUDEP Risk
Lundbeck will also present preclinical data demonstrating bexicaserin's potential to address sudden unexpected death in epilepsy (SUDEP), the most common cause of premature death in children and adults with epilepsy. In an audiogenic seizure model of SUDEP, bexicaserin significantly reduced both seizures and respiratory arrest.
Additional preclinical data will show the drug's impact on absence seizures, a seizure type that is often more difficult to treat, using the GAERS absence epilepsy model.
Addressing Critical Unmet Need
DEEs represent the most severe rare epilepsies, characterized by drug-resistant seizures, frequent epileptic activity on EEG, and developmental slowing or regression. The condition presents significant treatment challenges with few effective approved options available.
"Patients with DEEs represent a challenging group of rare epilepsies, with few effective approved treatment options," Luthman noted. "This marks a significant step forward in the potential to transform care for patients and address critical gaps in the treatment landscape."
The original PACIFIC trial was a Phase 1b/2a randomized, double-blind, placebo-controlled study that assessed bexicaserin in 52 participants aged 12 to 65 years with various types of DEEs at 34 sites across the United States and Australia. Participants had ≥4 countable motor seizures during a 28-day baseline period while on stable regimens of 1 to 4 concomitant antiseizure medications.
