Planned 2022 Clinical Trial Will Test LP352 in Reducing Seizures
Longboard Pharmaceuticals is planning to launch a Phase 1b/2a clinical trial early next year that will evaluate the company’s investigational therapy LP352 in adults with Dravet syndrome and other types of developmental and epileptic encephalopathies (DEEs).
The trial will test the therapy’s effectiveness in lessening seizures in patients with Dravet and other types of epilepsy characterized by episodes of prolonged seizures.
“We believe LP352 has the potential to reduce seizures in a broad range of severe and devastating, treatment-resistant epilepsies, and we look forward to advancing the program in patients living with these debilitating disorders,” Phil Perera, MD, chief medical officer at Longboard, said in a press release.
LP352 is an oral medication that activates a protein receptor called the 5-HT2c receptor. According to Longboard, the investigational medicine is designed to modulate the activity of a signaling molecule in the brain called GABA, and thereby reduce the abnormal nervous system activity that characterizes seizures.
A recently completed Phase 1 clinical trial tested LP352 in healthy volunteers, with 83 participants given one or multiple doses of the medication or a placebo.
The main goal was to assess the safety and tolerability of LP352 in people. The results were positive: in the multiple ascending dose portion of the trial, in which participants received several doses over time, most reported side effects, or adverse events, were mild or moderate in severity. The most common adverse event was a headache.
One serious adverse event, of anxiety, was reported in a participant who got the maximum planned dose of LP352.
Overall, the safety profile of the investigational medicine was generally consistent with the expected effects of a medication that works by activating the 5-HT2c receptor.
Also of note, participants in the trial exhibited dose- and exposure-dependent increases of prolactin. In other words, participants who received higher doses of LP352, and/or were given the medication for a longer time, had higher levels of prolactin in their bodies.
Prolactin is a hormone that, as its name suggests, is best-known for promoting lactation. Increased levels of prolactin with higher doses and exposures of LP352 suggest that the medication is activating 5-HT2c receptors in the brain as intended, according to Longboard.
“We are encouraged by the initial safety and tolerability characteristics of LP352 observed in the trial and that it appears to have a potent effect on the 5-HT2c pathway,” Perera said.
DEEs are a group of disorders characterized by both seizures and encephalopathy — any brain disease that alters brain function or structure. Most such disorders lead to significant developmental delays or a loss of developmental skills among patients.
Outside of Dravet syndrome, LP352 is being developed as a potential treatment for DEEs including Lennox-Gastaut syndrome, tuberous sclerosis complex, and CDKL5 deficiency disorder.