Praxis Precision Medicines, Inc. (PRAX) has received Rare Pediatric Disease Designation (RPDD) from the U.S. Food and Drug Administration (FDA) for relutrigine in the treatment of Dravet syndrome. This designation underscores the potential of relutrigine as a novel therapeutic option for this severe and often treatment-resistant form of epilepsy that begins in infancy. The RPDD may allow Praxis to obtain a priority review voucher upon FDA approval, potentially expediting the review of future drug applications.
Dravet syndrome is a genetic developmental and epileptic encephalopathy (DEE) typically emerging within the first year of life. It is characterized by frequent, prolonged seizures that are often resistant to treatment. Beyond seizures, Dravet syndrome can lead to intellectual disability, developmental delays, movement and balance difficulties, speech and language impairments, and an increased risk of early mortality, including sudden unexpected death in epilepsy (SUDEP).
Relutrigine: A Novel Approach to DEE Treatment
Relutrigine (PRAX-562) is a first-in-class small molecule being developed for DEEs. It functions as a preferential inhibitor of persistent sodium current, which has been identified as a key driver of seizure symptoms in SCN2A-DEE and SCN8A-DEE. The drug's mechanism involves modulating sodium channels, exhibiting selectivity for disease-state sodium channel (NaV) hyperexcitability. Preclinical studies have demonstrated dose-dependent inhibition of seizures, even achieving complete control of seizure activity in SCN2A, SCN8A, and other DEE mouse models.
Marcio Souza, president and chief executive officer of Praxis, stated, "We are thrilled to have been granted rare pediatric disease designation for relutrigine in Dravet syndrome... The designation builds upon encouraging clinical data demonstrating relutrigine’s ability to reduce seizure frequency and improve overall seizure control, highlighting our dedication to advancing innovative therapies that can significantly impact quality of life for those with limited treatment options."
Clinical Data and Future Trials
Praxis previously shared results from cohort 1 of the EMBOLD study, evaluating relutrigine in SCN2A and SCN8A patients. The data, presented at the 2024 American Epilepsy Society Annual Meeting, showed a placebo-adjusted monthly motor seizure reduction of 46% during the double-blind period. Over 30% of patients achieved seizure freedom while on relutrigine, and meaningful gains were observed in alertness, communication, and seizure severity. Furthermore, a 77% reduction in median seizure rate was seen for patients in the long-term extension.
Based on these findings, Praxis has initiated and is enrolling patients in a second, registrational cohort for SCN2A and SCN8A patients, with topline results expected in the first half of 2026. Additionally, Praxis plans to initiate an all-DEE trial (EMERALD), inclusive of Dravet syndrome, in the first half of 2025.
Relutrigine has already received Orphan Drug Designation (ODD) and RPDD from the FDA, as well as ODD from the European Medicines Agency for the treatment of SCN2A-DEE and SCN8A-DEE.
