Encoded Therapeutics reported durable seizure reduction, early neurodevelopmental improvements, and favorable safety with ETX101 in SCN1A-positive Dravet syndrome at ASGCT 2026.
Written by: Chikkula Pavan Kumar, Pharm D
Reviewed By: Pharmacally Editorial Team
Encoded Therapeutics presented updated interim findings from its ongoing POLARIS clinical development program evaluating ETX101, an investigational AAV9-based gene regulation therapy for SCN1A-positive Dravet syndrome, at the American Society of Gene & Cell Therapy (ASGCT) 2026 Presidential Symposium.
The expanded dataset included additional patients, early data from the top dose level (DL4), and longer-term follow-up, supporting ETX101’s potential as a one-time disease-modifying therapy for this severe pediatric neurological disorder.
Dravet syndrome is a rare developmental and epileptic encephalopathy primarily caused by pathogenic variants in the SCN1A gene. The disease is associated with recurrent drug-resistant seizures, developmental delay, cognitive impairment, behavioral abnormalities, and reduced quality of life, while current therapies mainly focus on seizure management.
ETX101 is an investigational AAV9-based precision gene regulation therapy designed to increase endogenous SCN1A expression and restore sodium channel function in inhibitory interneurons. Unlike traditional gene replacement approaches, ETX101 targets the underlying disease mechanism through a single intracerebroventricular injection designed to provide long-term benefit.
The POLARIS program comprises ongoing Phase 1/2 studies, including ENDEAVOR Part 1 (US, NCT05419492), EXPEDITION (UK, NCT06283212), and WAYFINDER (Australia, NCT06112275), evaluating ETX101 in infants and young children with SCN1A-positive Dravet syndrome.
Interim ASGCT 2026 findings demonstrated robust, dose-dependent antiseizure activity with durability through 52 weeks. From Week 5 through Week 52, children with highly treatment-resistant disease receiving optimized antiseizure therapies achieved a 76% median reduction in monthly countable seizure frequency at DL3. Early DL4 data showed continued dose-dependent activity, with the strongest responses observed in patients who did not receive sirolimus, which investigators said may dampen therapeutic signaling by reducing protein expression. Safety outcomes were comparable across groups.
Investigators also reported clinically meaningful improvements in adaptive behavior, including receptive and expressive communication, motor function, self-care, and social interaction. In children treated before age 2, cognitive gains emerged as early as Week 16 and continued through Week 52, with developmental trajectories generally consistent with neurotypical development.
ETX101 was well tolerated across all four dose levels, with no treatment- or procedure-related serious adverse events reported. The most common treatment-related adverse events were asymptomatic transaminase elevations that resolved in all participants.
ETX101 has received FDA Breakthrough Therapy, RMAT, Fast Track, Rare Pediatric Disease, and Orphan Drug designations.
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About the Writer
Chikkula Pavan Kumar (LinkedIn), PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication