Elsunersen

There is no approved treatment for SCN2A encephalopathy. Praxis is developing 2 drugs for it with different jobs: relutrigine, an oral sodium channel modulator for SCN2A and SCN8A encephalopathy that is under FDA review with a December 27, 2026 decision date, and elsunersen, which lowers the amount of SCN2A channel and is aimed only at gain-of-function disease. If both reach the market, a child with a gain-of-function variant could in principle be a candidate for either or both, and that sequencing question has not been studied. The company also has a preclinical antisense program, PRAX-100, aimed at loss-of-function SCN2A variants.

In gain-of-function SCN2A encephalopathy the Nav1.2 sodium channel is overactive, so the brain makes too much electrical activity from a channel that works too well. An antisense oligonucleotide is a short strand of synthetic genetic material that pairs with the messenger RNA for a specific gene and marks it for destruction, so the cell makes less of that protein. Elsunersen is designed to selectively decrease SCN2A gene expression, which lowers the number of overactive channels. Because that approach reduces the channel rather than blocking it, it is intended only for variants that make the channel overactive, not for the loss-of-function variants linked to autism, where lowering the channel further could be harmful. Antisense drugs do not cross from the blood into the brain, so elsunersen is given by lumbar puncture into the spinal fluid, the same route as nusinersen (Spinraza) for spinal muscular atrophy.

In Part A of the EMBRAVE study, Praxis reported no drug-related serious adverse events, no discontinuations and no signs of neuroinflammation at doses up to 8 mg, and most treatment-emergent adverse events were mild or moderate. Individual side effect rates have not been published. Intrathecal injection itself can cause headache, back pain and, rarely, infection or bleeding at the injection site, and young children often need sedation for the procedure.

EMBRAVE Part A (NCT05737784) randomized 9 children aged 2 to 12 with early-seizure-onset SCN2A developmental and epileptic encephalopathy 3 to 1 to elsunersen or a sham procedure every 4 weeks for 24 weeks, followed by an open-label extension. Elsunersen produced a 77% sham-adjusted reduction in monthly seizures from baseline (p 0.015, 95% CI 33 to 92); 71% of treated children had more than a 50% reduction in seizures and 57% had at least a 28-day period of seizure freedom during the 6 months of treatment. Praxis announced the results on April 6, 2026. The pivotal EMBRAVE3 study (NCT07019922) was converted after discussions with the FDA to a single-arm, baseline-controlled design in which every enrolled child receives elsunersen for 24 weeks and then a further 24 weeks; it is enrolling about 30 patients (the trial registry allows up to 40) from birth to age 18, with the primary analysis measuring the change from baseline in countable motor seizures and topline results expected in 2027.

Elsunersen came out of a collaboration between Praxis, Ionis Pharmaceuticals, which pioneered antisense medicines, and RogCon. It holds Orphan Drug and Rare Pediatric Disease designations from the FDA and Orphan Drug and PRIME designations from the EMA. On June 22, 2026 the FDA granted Breakthrough Therapy designation on the strength of the EMBRAVE Part A data, and Praxis confirmed the single-arm design for the pivotal study at the same time.