Relutrigine

No drug is approved specifically for SCN2A or SCN8A encephalopathy. Children are treated with combinations of existing anti-seizure medicines, and for the gain-of-function forms the sodium channel blockers such as phenytoin, carbamazepine and oxcarbazepine are often the most useful, though they can worsen seizures in children whose channel is underactive. Relutrigine would be the first therapy approved for these conditions and, if the label follows the trial, the first built around the persistent sodium current. A separate Praxis drug, elsunersen, takes the antisense route for SCN2A gain-of-function disease and is in a pivotal study.

SCN2A and SCN8A make 2 of the sodium channels that let brain cells fire. In the gain-of-function forms of these epilepsies the channels stay open too long and leak a steady trickle of sodium, called the persistent sodium current, that keeps neurons over-excited and seizure-prone. Standard sodium channel blockers act on the channel's normal signaling as well as the leak. Relutrigine was designed to prefer the persistent current, so it dampens the leak that drives seizures while leaving more of the normal signaling alone. Praxis describes it as a functional state-selective sodium channel modulator.

In the EMBOLD study, Praxis reported no drug-related serious adverse events, and treatment-related adverse events were predominantly mild or moderate. The company has not published the rates of individual side effects in its announcements, and there is no US label yet, so the warnings and monitoring plan are not known. The FDA told Praxis at the mid-cycle review in 2026 that it had identified no major safety or efficacy concerns to that point.

EMBOLD (NCT05818553) is a Phase 2/3 study in children and young people aged 1 to 18 with early-onset SCN2A or SCN8A developmental and epileptic encephalopathy. In the double-blind part, participants were randomized to relutrigine for 16 weeks or to relutrigine for 12 weeks followed by 4 weeks of placebo, then continued into an open-label extension of up to 144 weeks. A pre-specified interim analysis in November 2025 led the data monitoring committee to recommend stopping the study early for what Praxis described as overwhelming efficacy. In the results presented at the American Epilepsy Society meeting on December 6, 2025, the 51 patients on relutrigine had a 53% placebo-adjusted reduction in seizures over 16 weeks (p below 0.0002), a 66% increase in motor seizure-free days (p 0.034), and statistically significant improvements in clinician and caregiver global impression scores. Praxis is also running EMERALD, a trial of relutrigine across about 200 patients with more than 50 different genetic epilepsies, with results expected in the fourth quarter of 2026 and a possible supplemental application in 2027.

Praxis developed relutrigine as part of its sodium channel program. The FDA granted Breakthrough Therapy designation for SCN2A and SCN8A DEE in July 2025, alongside Orphan Drug and Rare Pediatric Disease designations that also cover Dravet syndrome, and the EMA granted orphan designation. After EMBOLD stopped early in November 2025, Praxis submitted the new drug application by February 2026; the FDA accepted it for priority review on March 30, 2026 with a target action date of September 27, 2026. On June 29, 2026 the FDA extended the review by 3 months to December 27, 2026 after Praxis submitted additional sensitivity analyses of the existing data, which the agency classed as a major amendment; no new studies were requested and no safety or manufacturing concerns were raised. In August 2026 Praxis said the mid-cycle meeting had been completed with no major concerns, no advisory committee is planned, and inspections of the trial sites had closed without observations.