PACIFIC study of LP352 for epilepsies hits enrollment target
52 patients will test its safety, tolerability, ability to reduce seizure frequency
Longboard Pharmaceuticals has finished enrolling patients in PACIFIC, its Phase 1b/2a clinical study of LP352, an investigational oral serotonin receptor agonist for Dravet syndrome and other types of developmental and epileptic encephalopathies (DEEs).
With 52 patients enrolled in 30 sites in the U.S. and Australia, the study’s main goals are to see how safe and well tolerated LP352 is versus a placebo and if it can reduce how often seizures happen when given three times a day for up to 75 days, or 2.5 months.
“Completing enrollment … is a tremendous milestone for Longboard and we are very pleased to see strong interest from the DEE patient community, underscoring the great unmet need that remains,” Randall Kaye, MD, Longboard’s chief medical officer, said in a press release.
Those who finish PACIFIC (NCT05364021) can take part in an open-label Phase 2 extension study (NCT05626634) that will test LP352 for up to 52 weeks. Top-line data, expected by year’s end, are likely to inform a planned Phase 3 study’s design.
“I look forward to seeing the PACIFIC data and the potential of LP352,” said Dennis Dlugos, MD, the study’s principal investigator. Dlugos is a pediatric neurologist at Children’s Hospital of Philadelphia and vice president and officer of the Epilepsy Study Consortium.
Dravet, other DEEs explained
Children with DEEs experience a delay in development or lose skills they’ve already learned. They also have frequent seizures, sudden bursts of excessive electrical activity in the brain, which may delay development even more.
Like other DEEs, Dravet syndrome causes long-lasting seizures that usually begin early in infancy and recur over a lifetime. They’re often refractory, meaning they’re difficult to control with available medications.
“I am excited about the innovative approach of conducting clinical research in DEEs more broadly given the significant unmet need and limited access to novel and targeted therapies that exists in the majority of patients living with refractory epilepsies,” Dlugos said.
LP352 is designed to mimic the effects of serotonin on 5-HT2C, a receptor in the brain and spinal cord. Serotonin, or 5-hydroxytryptamine (5-HT), is a chemical that carries signals between nerve cells, activating receptors around the body.
By activating 5-HT2C, LP352 should modulate gamma aminobutyric acid (GABA), which helps reduce the brain’s electrical activity, according to the company.
Because LP352 doesn’t activate other receptors, it’s said to be “specific” to 5-HT2C. This means it may reduce seizures in Dravet syndrome and other types of DEEs while avoiding the common side effects of less-specific serotonin agonists.
In a Phase 1 study of 83 healthy volunteers who received either LP352 or a placebo, most reported side effects were mild to moderate. Its safety profile aligned with expectations for a serotonin agonist that activates the 5-HT2c receptor.
What will PACIFIC study test?
PACIFIC will test LP352 in adults and adolescents, ages 12 and up, who’ve been having at least four seizures each month during the three months before screening despite being on stable anti-seizure medications.
The patients will be randomly assigned to either LP352 or a placebo. After about a month (baseline), they’ll enter a 15-day period where LP352 will be titrated up to the highest tolerated dose, followed by a 60-day maintenance period, and a 15-day taper period.
Side effects, suicide ideation, symptoms of depression, and changes in countable motor seizures, which cause muscles to tighten, will be evaluated at baseline and at the end of the maintenance period, or after 2.5 months of treatment.
“We would like to thank the entire DEE community, including participants, their families and the advocates, as well as the investigators, sites and coordinators for their participation and continued collaboration. This achievement brings us one step closer to helping people living with [DEEs],” Kaye said.
The study was also open to patients with Lennox-Gastaut syndrome (LGS), a severe form of epilepsy that causes many different types of seizures, as well as other DEEs.
“The inclusive nature of the PACIFIC Study is unique and exciting, especially given that people living with certain DEEs have not had access to newer therapies and clinical trials,” said Tracy Dixon-Salazar, PhD, executive director of the LGS Foundation.