Harmony Biosciences Holdings, Inc. announced the presentation of initial open-label extension (OLE) data from the company's ongoing Phase 3 ARGUS trial investigating EPX-100 (clemizole hydrochloride) for the treatment of Dravet syndrome (DS), which showed clinically meaningful reductions in seizure activity in participants with DS along with a favorable benefit-risk profile. Data from the eighteen participants in the OLE trial with at least six months' exposure to EPX-100 demonstrated the following: A median reduction of approximately 50% in countable motor seizure frequency per 28 days (CMS-28); 50% of these participants achieved at least a 50% reduction in CMS-28; EPX-100 was generally well-tolerated in participants receiving treatment for more than two years and approaching three years in the OLE phase; The most common treatment emergent adverse events (> 5%) were seizures, pyrexia and upper respiratory tract infection; There were no significant gastrointestinal adverse events (2%) and no additional laboratory testing or special monitoring is being performed in the trial. These data suggest a positive emerging benefit-risk profile for EPX-100, supported by clinically meaningful reduction in seizure frequency and a favorable safety/tolerability profile.
EPX-100, clemizole hydrochloride, is an investigational product under development for the treatment of DraveT syndrome (DS) and Lennox-Gastaut syndrome (LGS). EPX-100 acts by targeting central 5-hydroxytryptamine 2 (5HT-2) serotonin receptors to modulate serotonin signaling. EPX-100 is administered orally twice a day in a liquid formulation and has been developed based on a proprietary phenotype-based zebrafish drug screening platform.
These scn1Lab mutant zebrafish replicate the genetic etiology and phenotype observed in the majority of individuals with DS. The scn1Lab mutant z zebrafish model that expresses voltage gated sodium channels has been used for high-throughput screening of compounds that modulate Nav1.1 in the central nervous system. Dravet syndrome (DS) is a severe and progressive developmental epileptic encephalopathy that causes significant impact on patient functioning.DS begins in the first year of life and is characterized by high seizure frequency and severity, intellectual disability, and an increased risk of sudden unexpected death in epilepsy (SUDEP).
Approximately 85% of Dravet syndrome cases are caused by de novo loss-of-function (LOF) mutations in a voltage-gated sodium channel gene, SCN1A.DS has an estimated incidence rate of 1:15,700 in the US. Lennox-Gastaut Syndrome (LGS) is a rare and drug-resistant epileptic syndrome (LGS) is a Rare and drug-resistant epileptic epilepsy (SUDEP).
