FDA Grants Breakthrough Therapy Status to Relutrigine for Seizures in SCN2A and SCN8A Encephalopathies

Praxis Precision Medicines, a clinical-stage biopharmaceutical company focused on neurological disorders, has achieved a significant milestone with its drug candidate, relutrigine. The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to relutrigine for pediatric use in treating SCN2A and SCN8A developmental and epileptic encephalopathies (DEEs). This decision was influenced by promising results from the Phase 2 EMBOLD trial.

Relutrigine, a sodium channel modulator, has shown remarkable efficacy in reducing seizures among patients in the EMBOLD cohort 1 study. The cohort involved a severely affected population, most of whom had not responded to at least three prior treatments. The open-label extension of the trial demonstrated an impressive average seizure reduction of approximately 90% and a significant increase in seizure-free intervals, greatly enhancing the quality of life for both patients and their caregivers.

Praxis is now advancing with the EMBOLD cohort 2 trial, aiming to provide topline results by the first half of 2026. This will be followed by a New Drug Application (NDA) submission. The BTD, alongside the Rare Pediatric Disease Designation, emphasizes the potential for expedited development and approval of relutrigine.

Additionally, Praxis has initiated the EMERALD study, a 16-week, placebo-controlled trial evaluating relutrigine across various DEEs. This study seeks to comprehensively assess the drug's ability to reduce seizures in patients with different types of developmental epileptic disorders.

The data from the EMBOLD study were crucial in securing BTD. During the trial's double-blind phase, a placebo-adjusted monthly motor seizure reduction of 46% was observed, with over 30% of patients achieving seizure freedom on relutrigine. Enhancements in alertness, communication, and seizure severity were also noted by both clinicians and caregivers. In the ongoing open-label extension, patients experienced a sustained 90% reduction in seizures and a significant increase in seizure-free days compared to the baseline period. Importantly, no new safety concerns or serious adverse events related to the drug were reported.

Relutrigine, also known as PRAX-562, operates as a preferential inhibitor of persistent sodium current, a key factor in severe DEEs. Its mechanism aligns with the selective modulation of hyperexcitable sodium channels, which is crucial for controlling seizure activity. Preclinical studies have shown dose-dependent seizure inhibition, and the drug has been well-tolerated in previous Phase 1 studies.

Praxis has received additional recognitions for relutrigine, including Orphan Drug Designation and Rare Pediatric Disease Designation from the FDA, as well as designations from the European Medicines Agency for SCN2A-DEE and SCN8A-DEE, and Dravet syndrome.

Praxis Precision Medicines is leveraging genetic insights to develop therapies for central nervous system disorders characterized by an imbalance in neuronal excitation and inhibition. The company employs a proprietary platform to discover and develop treatments for rare and common neurological conditions. With a diverse pipeline, Praxis aims to address various epilepsy and movement disorders.