Early onset SCN2A developmental and epileptic encephalopathy (SCN2A-DEE) is a rare, severe disorder caused by gain-of-function mutations in the SCN2A gene. Elsunersen is an intrathecally administered ASO in development for early onset SCN2A-DEE, with emerging clinical data highlighting its potential to be disease modifying.

Elsunersen has been administered in Germany since March 2023 to a preterm infant (29+4 weeks gestation) diagnosed prenatally with a pathogenic SCN2A variant. The patient was in constant, life-threatening status epilepticus (SE), with only partial effect of high-dose sodium channel blockers. A 9-year-old patient with early onset SCN2A-DEE has been receiving elsunersen in Australia since December 2023, following a history of refractory seizures, global cerebral atrophy, global developmental delay, frequent oculogyric movement, and severe dystonia while awake. Three patients with SCN2A-DEE in the US, two from the completed EMBRAVE study and a 4-month-old infant, have received emergency access to elsunersen since March–May 2024.

There have been no reported drug-related severe or serious AEs following ongoing administration of any dose in any patient, with procedure and dosing well tolerated across >80 doses globally. To date, elsunersen has demonstrated durable seizure reduction, resolution of SE, and meaningful quality-of-life improvements across emergency use cases. In the German patient, early dosing led to SE cessation and sustained seizure stability with no neurodevelopment worsening through age 2 years. The Australian patient demonstrated marked reduction in clinical and electrographic seizures and notable QoL improvement within the first year, with ongoing stability. All US children maintain seizure stability, with two children demonstrating further alongside functional improvements (oxygen therapy discontinuation and weaning from a ketogenic diet). 

Elsunersen’s clinical experience to date demonstrates a well-tolerated, consistent and meaningful therapeutic response. Ongoing follow up will determine long-term effect on seizures and associated comorbidities.