DEEs are a group of chronic, devastating conditions presenting during infancy and characterized by severe, frequent seizures, developmental delay or regression, and increased early mortality. Relutrigine is a differentiated functional state sodium channel modulator in late-stage development for broad DEEs, with demonstrated superior selectivity for disease-state hyperexcitability, a known cause of seizure manifestation across all DEEs. 

EMERALD is a multicenter, double-blind, placebo-controlled Phase 3 study enrolling ~160 eligible male and female participants aged 2-65 years with a DEE diagnosis and onset of seizures <12 years old. It will include an initial Screening Period (including 28-day Baseline Observation), Part A (Double-Blind Treatment Period, 16 weeks), Part B (OLE Treatment Period, 32 weeks), and Safety Follow-up. In Part A, participants will be randomized (1:1) to receive either relutrigine (1mg/kg/day starting dose; dose modification permitted up to 1.5mg/kg/day) or placebo QD. Participants will have the option to undergo study assessments at home, in-clinic or as a combination of both.   

The primary endpoint will assess efficacy based on change in motor seizure frequency. Secondary endpoints will include the proportion of patients achieving >50% reduction in seizure frequency and seizure-free days from baseline, as well as change in clinician and caregiver-reported outcomes. Secondary endpoints will also assess TEAE incidence and severity, with further exploratory endpoints assessing PK and additional efficacy outcomes. OLE endpoints will capture long-term safety, tolerability and efficacy outcomes. 

Recent findings from the EMBOLD study demonstrated well-tolerated, pronounced seizure reduction and unprecedented seizure-free status in patients with SCN2A-DEE and SCN8A-DEE, with emerging preclinical data highlighting robust, differentiated efficacy in multiple DEE models. Findings from the EMERALD study are anticipated to provide further evidence for relutrigine’s potential to be a first- and best-in-class small molecule for DEEs.