Summary 1: Gene Therapy Shows Promise in Early Dravet Trials

Preliminary results from a pioneering gene therapy trial suggest a potential one-time treatment for Dravet syndrome may be on the horizon. Researchers presented interim findings from the POLARIS Phase 1/2 program at the American Epilepsy Society’s annual meeting in Atlanta, detailing the first clinical data for ETX101, an investigational gene regulation therapy.

ETX101 represents a novel approach to treating Dravet syndrome, a severe epileptic encephalopathy affecting young children. The therapy uses an adeno-associated virus to deliver genetic material designed to increase production of Nav1.1 protein specifically in GABAergic interneurons, addressing the underlying cellular dysfunction in Dravet syndrome. More than 90% of Dravet cases stem from loss-of-function variants in the SCN1A gene, which encodes this critical sodium channel protein.

The ongoing program comprises three open-label, dose-escalation studies conducted across the United States, Australia, and the United Kingdom. Eligible participants range from 6 months to 7 years of age, have confirmed pathogenic SCN1A variants, and experienced their first seizure between 3 and 15 months of age. The therapy is administered through a single intracerebroventricular infusion.

As of June 2025, eleven participants had received ETX101 with follow-up extending to 58 weeks. No treatment-related serious adverse events or dose-limiting toxicities have been reported. Early efficacy data revealed dose-dependent seizure reduction, with the highest dose tested achieving an 87% median reduction in monthly seizure frequency during the observation period from week 5 through at least week 12 post-treatment. Participants also experienced increased seizure-free days and reduced need for rescue medications.

Lead investigator Dr. Joseph Sullivan from the University of California San Francisco noted this represents the first potential one-time, disease-modifying treatment approach for Dravet syndrome. Dose escalation continues as researchers work to establish optimal efficacy and long- term durability of response.

Reference: 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. Abstract 1.308. Presented at: American Epilepsy Society Annual Meeting; December 6, 2025; Atlanta, GA. https://aesnet.org/abstractslisting/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