Encoded Therapeutics' Gene Therapy Shows Promise in Dravet Syndrome Trial

Encoded Therapeutics has reported encouraging results from its phase 1/2 trial of ETX101, a gene therapy for Dravet syndrome, paving the way for a pivotal study in 2026. The California-based biotech presented data at the American Epilepsy Society Annual Meeting, demonstrating significant seizure reduction and neurodevelopmental improvements in pediatric patients.

Impressive Efficacy and Safety Profile

ETX101, an AAV9-based therapy designed to boost expression of the SCN1A gene, showed a 78% median reduction in monthly countable seizure frequency at the third dose level. This data comes from a seven-month monitoring period of three patients who were receiving anti-seizure medications at baseline.

Importantly, no treatment-related serious adverse events were reported across all four dose levels tested, suggesting a favorable safety profile for the gene therapy.

Neurodevelopmental Gains and Early Intervention

The trial also yielded promising neurodevelopmental data. All four children on the two lowest doses with 52 weeks of follow-up demonstrated "meaningful positive divergence" from untreated children in a natural history study. Improvements were most notable in receptive and expressive communication and motor function, followed by self-care and social interaction.

Particularly striking were the results in younger patients. Four of the five children treated before two years of age showed substantial acceleration of cognitive skill acquisition as early as 16 weeks, with progressive gains through 52 weeks of observation. This finding suggests that ETX101 may be most beneficial when administered to children under two years of age, potentially influencing the therapy's future positioning in the treatment landscape.

Looking Ahead: Pivotal Trial and Financial Considerations

Encoded Therapeutics is now on track to initiate a pivotal study of ETX101 in 2026. Before that, the company expects to report efficacy data from the fourth and final dose cohort next year, which could potentially surpass the already impressive results seen in lower doses.

However, the road to commercialization may present financial challenges. As of February, the company's cash runway extended into the third quarter of 2026, reflecting a recent 29% reduction in workforce and a decision to focus resources on ETX101. To fund the pivotal program, Encoded will likely need to secure additional funding or establish a strategic partnership.

As the development of ETX101 progresses, it enters a competitive landscape that includes other potential disease-modifying treatments for Dravet syndrome. Notably, Stoke Therapeutics is currently enrolling patients aged 2 to 18 years in a phase 3 trial of zorevunersen, an antisense oligonucleotide partnered with Biogen. This positions zorevunersen to potentially become the first disease-modifying Dravet drug to market, ahead of Encoded's gene therapy.