March 27, 2026-
Encoded Therapeutics has announced regulatory progress for ETX101, an investigational AAV9-based gene regulation therapy for SCN1A-positive Dravet syndrome, following a successful Initial Comprehensive Multidisciplinary Regenerative Medicine Advanced Therapy (RMAT) meeting with the U.S. Food and Drug Administration (FDA). During the meeting, the company achieved alignment with the FDA on the pivotal study design supporting a planned Biologics License Application (BLA) submission.
The pivotal study, ENDEAVOR Part 2, will evaluate a single administration of ETX101 in 30 infants and young children aged 6 months to under 4 years with SCN1A+ Dravet syndrome. The randomized, double-blind study will compare treatment with a sham delayed-treatment control over a 52-week period. The primary endpoint will assess reduction in monthly countable seizure frequency (MCSF), while a key secondary endpoint will evaluate cognitive development using the Bayley Scales of Infant and Toddler Development (Bayley-4).
In parallel, Encoded has initiated ENDEAVOR Part 1B, an expansion of the ongoing Phase 1/2 open-label study to include older patients aged 4 to under 18 years. This portion of the study will focus primarily on safety and tolerability, while also exploring preliminary signals of efficacy, including changes in seizure frequency and improvements in neurodevelopmental outcomes.
ETX101 is designed as a precision AAV9 gene regulation therapy that increases the expression of the SCN1A gene, which encodes a sodium channel critical for proper neuronal signaling. Mutations in SCN1A disrupt inhibitory interneuron function and lead to the severe seizures and neurodevelopmental challenges characteristic of Dravet syndrome. By restoring SCN1A expression in these neurons, ETX101 aims to address the underlying cause of the disease and potentially modify its progression.
The therapy is administered through a single intracerebroventricular (ICV) injection, enabling delivery of the AAV9 vector directly into the central nervous system to achieve widespread neuronal transduction.
The pivotal trial design is supported by encouraging clinical findings from the POLARIS Phase 1/2 study, which reported significant and durable reductions in seizure frequency along with improvements in neurodevelopmental outcomes in treated participants. These results helped inform the design of the ENDEAVOR pivotal trial.
Enrollment in the pivotal study is expected to complete by the end of 2026, with initial clinical data anticipated in 2027. Early data from the ENDEAVOR Part 1B expansion study are expected in late 2026.
Dravet syndrome is a severe genetic epilepsy that begins in infancy, characterized by frequent drug-resistant seizures along with developmental delays, cognitive impairment, and behavioral challenges. With multiple regulatory designations—including Breakthrough Therapy, RMAT, Fast Track, Rare Pediatric Disease, and Orphan Drug status from the FDA—ETX101 represents a promising AAV-based gene therapy approach aimed at providing long-term disease modification for children affected by this devastating condition.
