Pivotal trial of Dravet syndrome gene therapy begins, now enrolling children
Encoded hopes to use EXT101 study results to seek treatment's approval
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Encoded Therapeutics announced that the first participant has been dosed in a pivotal clinical trial testing ETX101, the company’s experimental one-time gene therapy for Dravet syndrome, which is recruiting children and adolescents with this severe form of epilepsy.
The pivotal study is the second part of the ENDEAVOR clinical trial (NCT05419492), designed to test the treatment candidate’s safety and effectiveness. It’s now enrolling children with Dravet ages 6 months to 17 years at sites in the U.S. and Australia. Sites in the U.K. are also expected to enroll patients, but as of mid-April, they had not yet begun recruitment.
To be eligible for ENDEAVOR, participants must have a confirmed mutation in the SCNA1Â gene and be on at least one antiseizure medication. Participants also must have experienced their first seizure between the ages of 3 and 15 months.
The second part of the study specifically aims to enroll 30 children aged 6 months to 4 years. Participants will be randomly assigned to receive ETX101 or a sham procedure, with the main goal of tracking the therapy’s effect on seizure frequency over about a year of follow-up. Participants initially given the sham will then have the opportunity to receive active therapy.
Encoded recently aligned with the U.S. Food and Drug Administration (FDA) on plans for the pivotal study. Assuming the results are positive, the company hopes to use the findings as a basis for seeking approval for ETX101. The pivotal study is expected to finish recruitment this year, with results anticipated in 2027, according to a press release from Encoded.
In parallel with the pivotal study, Encoded said that it has also started dosing in an expansion phase of the first part of the ENDEAVOR trial. That part of the study is testing ETX101 in children with Dravet who are ages 4 and older.
Adam Numis, MD, principal investigator for the ENDEAVOR studies at the University of California, San Francisco, said that having both parts of the study active “reflects our dedicated effort to understand [ETX101’s] potential to meaningfully alter disease trajectory in the broader patient population.”
Gene therapy designed to treat underlying cause of Dravet
Dravet is mainly caused by mutations in the SCN1A gene. Reduced activity of this gene disrupts neurological signaling, ultimately leading to seizures and other Dravet symptoms.
ETX101 is designed to boost SCN1A gene activity, thereby addressing the disease’s underlying cause. The one-time gene therapy is administered via infusion into fluid-filled cavities within the brain.
Interim data from two open-label Phase 1/2 clinical studies — EXPEDITION (NCT06283212) in the U.K. and WAYFINDER (NCT06112275) in Australia — have suggested that the therapy may reduce seizure frequency in Dravet children.
“This therapy is designed to target SCN1A and address the underlying genetic cause of disease,” Numis said. “Promising open-label data from the initial Phase 1/2 studies generated significant interest from the Dravet community, and dosing the first patients … in the pivotal and expansion studies is an important step forward for families affected by this disease.”
Encoded also announced that the FDA has selected ETX101 for its Chemistry, Manufacturing, and Controls Development and Readiness Pilot (CDRP) program. This initiative aims to help companies establish protocols for the commercial manufacturing of promising therapies in clinical development, so that, if a therapy is proven effective, there are systems in place to help bring it to market as soon as possible.
Earlier this year, the FDA named ETX101 a breakthrough therapy for Dravet. That designation is intended to speed development of promising therapies.
