Encoded Therapeutics Reports 78% Seizure Reduction with ETX101 Gene Therapy in Dravet Syndrome Trial
核心洞察
Encoded Therapeutics (搜索)' ETX101 gene therapy achieved a 78% median reduction in seizures at the third dose level in children with Dravet syndrome (搜索) through seven months of observation.
The treatment demonstrated clinically meaningful neurodevelopmental improvements across multiple measures, with substantial cognitive skill acceleration evident by 16 weeks in children treated before age two.
ETX101 showed a favorable safety profile across all four dose levels with no treatment-related serious adverse events in 19 participants enrolled in the Phase 1/2 POLARIS program.
Encoded Therapeutics (搜索) announced positive interim results from its POLARIS clinical development program evaluating ETX101, an AAV9-based gene therapy, in children with SCN1A (搜索)+ Dravet syndrome (搜索). The data, presented at the American Epilepsy (搜索) Society Annual Meeting, showed substantial seizure reductions and neurodevelopmental improvements in this severe pediatric epilepsy disorder.
Significant Seizure Control Achieved
The Phase 1/2 trials demonstrated substantial antiseizure effects, with a 78% median reduction in monthly countable seizure frequency (MCSF) observed through seven months at the third dose level (3.3E12 vg/mL CSF) in three participants. These reductions occurred in drug-resistant participants already receiving optimal antiseizure medications during a developmental period typically associated with worsening seizure burden.
ETX101 is administered via a single intracerebroventricular injection into the cerebrospinal fluid, targeting the underlying cause of Dravet syndrome (搜索) by increasing SCN1A (搜索) expression in GABAergic inhibitory neurons (搜索). The treatment showed dose-dependent and sustained reductions in seizure frequency across the study population.
Neurodevelopmental Benefits Observed
Beyond seizure control, ETX101 demonstrated progressive and clinically meaningful neurodevelopmental gains measured by both the Vineland Adaptive Behavior Scales (VABS-3) and Bayley Scales of Infant and Toddler Development (Bayley-4) through 52 weeks of observation.
On VABS-3 assessments, four participants across the first two dose levels who reached 52 weeks of follow-up all showed meaningful positive divergence from untreated children in the ENVISION natural history study. The most notable improvements occurred in receptive and expressive communication and motor function, with significant progress also observed in self-care and social interaction.
Particularly striking results emerged in the youngest patients. Four out of five participants treated before two years of age showed substantial acceleration of cognitive skill acquisition as early as 16 weeks, with progressive gains continuing through 52 weeks of observation. This cognitive development rate represents an important deviation from the developmental slowing and eventual plateauing typically observed in Dravet syndrome (搜索).
"These results point to the possibility of a one-time treatment that not only reduces seizures, but also addresses the profound neurodevelopmental stagnation that affects the ability of children with Dravet syndrome (搜索) to communicate, learn, and function independently," said Joseph Sullivan, M.D., Professor of Neurology & Pediatrics at University of California, San Francisco, and Principal Investigator on the ENDEAVOR study.
Favorable Safety Profile Maintained
ETX101 demonstrated a favorable safety profile across all four dose levels tested (5.0E11, 1.9E12, 3.3E12, and 6.6E12 vg/mL CSF) in 19 participants, with no treatment-related serious adverse events reported. The most common treatment-related adverse events were expected transaminase elevations, a known AAV class effect, which were clinically asymptomatic and resolved in all participants.
Comprehensive Clinical Program Structure
The POLARIS program comprises three ongoing open-label, dose-escalation trials conducted across multiple countries: ENDEAVOR Part 1 in the US, EXPEDITION in the UK, and WAYFINDER in Australia. These Phase 1/2 trials evaluate ETX101 in children aged 6 months to 7 years with Dravet syndrome (搜索) caused by SCN1A (搜索) gene variants.
The interim results reported include safety data from all four dose levels and efficacy data for the first three dose levels, with a data cutoff of November 10, 2025. The primary objective focuses on safety and tolerability assessment, while secondary objectives evaluate preliminary efficacy through seizure frequency changes and neurodevelopmental symptom improvements.
Addressing Critical Unmet Need
Dravet syndrome (搜索) affects approximately 35,000 people across the United States, United Kingdom, EU4, and Japan. This severe developmental and epileptic encephalopathy (搜索) begins in infancy, with most cases caused by SCN1A (搜索) gene variants resulting in reduced NaV1.1 (搜索) protein in the brain. The condition carries significant mortality risk, with up to one in five children dying before adulthood from Sudden Unexpected Death in Epilepsy (搜索) (SUDEP).
Currently, no approved disease-modifying therapies exist for Dravet syndrome (搜索), representing a significant unmet medical need. ETX101 has received multiple regulatory designations including Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug Designations from the FDA, as well as Orphan Designation from the EMA.
"While early, the emerging clinical impact of ETX101 underscores its potential as a one-time, disease-modifying medicine for Dravet syndrome (搜索)," said Kartik Ramamoorthi, Ph.D., Chief Executive Officer of Encoded Therapeutics (搜索). "We look forward to presenting efficacy data from the fourth and final dose level as we seek to advance ETX101 toward a pivotal clinical trial in 2026."