Overviewing Promising Phase 1/2 Data of Gene Therapy ETX101 in Dravet Syndrome: Joseph Sullivan, MD

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"Several children achieved developmental gains in 16 weeks that would typically take a full year in natural history. The magnitude of improvement in communication domains is something we have never seen before in Dravet syndrome."

The treatment landscape for Dravet syndrome (DS) continues to evolve as investigators explore approaches intended to target underlying SCN1A dysfunction, with gene replacement strategies among the earliest-stage modalities now entering human testing. These programs aim to address core elements of the disease biology that conventional antiseizure medications do not modify, yet they remain investigational and must be evaluated with careful attention to safety, dosing, and developmental impact in a vulnerable pediatric population.

At the 2025 American Epilepsy Society (AES) Annual Meeting, held October 5-9, in Atlanta, Georgia, new interim phase 1/2 data were presented from the POLARIS program of ETX101, an AAV9-based gene replacement therapy currently under evaluation in infants and young children with DS. The program includes 3 different trials, each with varying age cohorts, testing the safety, preliminary efficacy, and effects on neurodevelopmental issues. The new data, which included 19 patients followed up for at least 58 weeks, showed that the drug was well-tolerated, with dose-dependent anti-seizure effects observed.

During the meeting, NeurologyLive^® sat down with primary investigator Joseph Sullivan, MD, director of the Pediatric Epilepsy Center of Excellence at the University of California San Francisco, to discuss the findings in greater detail. Sullivan, an epilepsy expert and leader of several pivotal trials, reviewed safety observations across 4 dose tiers, early signals of seizure reduction that strengthen at higher doses, and the unexpected magnitude of developmental and cognitive improvements seen in treated children. Furthermore, Sullivan also outlined how these early results inform future dose selection and study design, and why the durability and breadth of benefit observed so far may represent a meaningful step toward disease modification in this population.

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REFERENCE
1. Sullivan J, Scheffer I, Howell K, et al. POLARIS Phase 1/2 Program Interim Safety and Preliminary Efficacy Results of ETX101, a One-Time Gene Regulation Therapy, in Young Children with Dravet Syndrome. Presented at: 2025 AES Annual Meeting; December 5-9; Atlanta, Georgia. ABSTRACT 1.308