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Relutrigine Shows Promise in Phase 2 EMBOLD Study of SCN2A-DEE and SCN8A-DEE
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Key Takeaways
- Relutrigine showed a 46% placebo-adjusted reduction in motor seizures in SCN2A and SCN8A-DEE patients during the EMBOLD trial.
- The investigational agent was well tolerated, with no serious adverse events and 33% of patients achieving seizure freedom.
Treatment with relutrigine resulted in a 46% placebo-adjusted reduction in motor seizures, along with a well-tolerated safety profile with adverse events that were mild to moderate.
Marcio Souza, MD, PhD
Data from the phase 2 EMBOLD trial revealed that treatment with relutrigine (Praxis Precision Medicines), an investigational agent, resulted in robust, short- and long-term improvements in motor seizures among patients with early onset SCN2A-developmental epileptic encephalopathy (DEE) and SCN8A-DEE. Based on the positive results of cohort 1, Praxis has initiated a second cohort of the EMBOLD study to be sufficient for registration, aiming to enroll 80 patients, with topline results in the first half of 2026.1
SCN2A and SCN8A are amongst the most severe and refractory forms of DEE, with an estimated prevalence of around 5000 patients in the US. These patients often experience lifelong symptoms, including severe seizures, movement disorders, developmental delays, and significant impacts on quality of life. Relutrigine, which has received orphan drug and rare pediatric designations from the FDA, is a first-in-class small molecule for the development of DEE as a preferential inhibitor of persistent sodium current.
Results from EMBOLD were presented at the 2024 American Epilepsy Society (AES) Annual Meeting, held December 6-10 in Los Angeles, California, by Silvana Frizzo, MD, medical director at Praxis. The multicenter, double-blind, placebo-controlled study featured 16 patients aged 2-18 who were randomly assigned 1:1 to either relutrigine QD for 16 weeks or relutrigine QD for 12 weeks or matching placebo QD for 4 weeks, with timing of placebo administration blinded for both participants and investigator.
Results revealed that treatment with the investigational agent resulted in a 46% placebo-adjusted reduction in motor seizures during the double-blind portion of the study, with significant reductions observed over single 28-day (27% [n = 8] vs placebo: 1.6% [n = 7]) and open-label extension (OLE; 75% [n = 8]) periods. At the time of submission, 33% of treated patients were seizure-free, with improvements around 30-70% in multiple domains of caregiver and clinician-reported scales. Overall, relutrigine was well tolerated, with mostly mild to moderate adverse events (AEs), no drug-related serious AEs, no dose reductions, and more than 50% of patients reaching 1 mg/kg/day.
Praxis originally announced topline results from EMBOLD in September, with data showing no patients discontinuing the trial because of AEs. On caregiver and clinician scales, patients showed improvement in disruptive behavior (caregiver: 29%; clinician: 23%), communication (43%; 31%), seizure severity and intensity (71%; 62%), and alertness (57%; 69%).2
At the time of the released data, 8 patients had completed at least one 28-day period in the long-term extension of EMBOLD. Within this group, these patients had a median reduction in motor seizures of 75%. Notably, 5 patients achieved a 28-day seizure free status while receiving relutrigine, compared with none on placebo.
"We are thrilled to see the combination of positive efficacy and tolerability of relutrigine for SCN2A and 8A, where there are no approved treatments. When comparing to the baseline rates, patients in EMBOLD had over 2,000 fewer seizures since the beginning of the study. This kind of remarkable impact keeps us focused on advancing our programs," Marcio Souza, MD, PhD, president and chief executive officer at Praxis, said in a statement following the topline data announcement.2 "Seizure freedom is the ultimate goal for patients, and we were humbled by the progress made with relutrigine during the EMBOLD study with over 30% of patients achieving this life-altering milestone."
Sodium channel blockers are used broadly by patients with DEEs. According to a recent company announcement, Praxis has decided to initiate a registrational study, dubbed EMERALD, in all DEEs, which is planned to begin in the first half of 2025 after alignment with regulators.3
Click here for more AES 2024 coverage.
REFERENCES
1. Frizzo S, Spar B, Dalby K, et al. Relutrigine demonstrates robust seizure reduction and seizure freedom in Dees: results from the EMBOLD study. Presented at: 2024 AES Annual Meeting; December 6-10; Los Angeles, CA. ABSTRACT 1.528
2. Praxis Precision Medicines announces positive topline results from the EMBOLD study in SCN2A and 8A developmental epilepsies, highlighting the disease-modifying potential of relutrigine. News release. Praxis Precision Medicines. September 3, 2024. Accessed December 5, 2024. https://www.globenewswire.com/news-release/2024/09/03/2939566/0/en/Praxis-Precision-Medicines-announces-positive-topline-results-from-the-EMBOLD-study-in-SCN2A-and-8A-developmental-epilepsies-highlighting-the-disease-modifying-potential-of-relutri.html
3. Praxis Precision Medicines Provides Corporate Update and Reports Third Quarter 2024 Financial Results. News release. Praxis Precision Medicines. November 6, 2024. Accessed December 5, 2024. https://investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-provides-corporate-update-and-14
