One-time gene therapy for severe child epilepsy cut seizures, maker says

Encoded Therapeutics says a one-time gene therapy reduced seizures and was followed by gains in learning and communication in young children with Dravet syndrome, a rare and severe form of epilepsy. The interim results, from 21 children, were presented at the European Society of Gene and Cell Therapy conference in Hamburg, Inside Precision Medicine reported on October 30.¹ The studies were small and had no comparison group, so they cannot yet show that the therapy caused the improvements.¹²

What happened

The therapy, called ETX101, is being tested in three early-stage trials. These are Phase 1/2 studies, which check first for safety and give a first look at whether a treatment might help.¹ Salvador Rico, Encoded’s chief medical officer, described the results at the conference.¹

The team treated 21 children aged six months to seven years. Each received a single injection into a ventricle, one of the fluid-filled spaces deep in the brain, and kept taking their usual seizure medicines.¹ Four different doses were tested.¹ According to the report, no serious side effects and no dose-limiting problems were seen, and the children showed fewer seizures and better communication, thinking and new skills.¹

Rico called the size of the seizure effect in such hard-to-treat children “really remarkable and without precedent”.¹ That is the company’s view of its own data.

The evidence so far

Seizures

The researchers counted seizures each month and compared that with the period before treatment. Results differed by dose, by group and by time period, and the groups were very small.

• An update presented in September at the European Epilepsy Congress in Athens gave figures for the two higher doses. Among 5 children at the third dose level, the median monthly seizure count fell by about 76% from week 5 to week 52 or their latest visit. Among 9 children at the highest dose, the median fall over the same window was about 60%.²
• Among children who had been followed for a full year, the median fall at month 12 was about 79% in 3 children at the third dose and about 89% in 5 children at the highest dose.²
• The Hamburg report described 3 children at the third dose with a median fall of about 76% through one year, and 4 children at the highest dose, given the steroid prednisolone but not the drug sirolimus, with about an 84% fall between enrollment and week 16.¹

The two reports group the children slightly differently, so their numbers do not line up exactly. An earlier analysis, presented in 2025, found a median 78% drop at week 32 in the small third-dose group, and less severe seizures, less rescue medicine and fewer hospital stays at lower doses.²

Development

Children with Dravet syndrome usually develop more slowly as they get older.¹ In children treated before age 2, scores on a standard test of infant and toddler thinking skills kept rising over up to 76 weeks. Encoded said their progress moved away from the stalled pattern seen in untreated children in an earlier tracking study called ENVISION, and approached the range expected for typical children.² A separate test of everyday skills showed gains in communication, movement, social skills and daily living, especially in understanding and using language and in motor skills, according to the company.²

“Rather than entering the expected pattern of stagnation, these patients are showing an acquisition of skills that is most consistent with typical development,” explained Rico. “This is suggesting that we may be rescuing learning abilities.”

¹

Safety

No serious side effects had been reported, but six children developed raised liver enzymes, a blood sign of liver stress.¹ The September report described no serious side effects linked to the treatment or the injection procedure, and said raised liver enzymes and low platelet counts, which caused no symptoms, cleared up without lasting effects.²

What it does not show yet

All three studies are open-label, meaning every child got the treatment and their families and doctors knew it, and none had a control group.¹ Without a group of untreated children followed the same way, it is hard to separate the therapy’s effect from other causes, such as changes in other care or the way seizure counts naturally rise and fall. NeurologyLive noted that randomized data, where children are assigned to groups by chance, will be needed to tie the seizure and development changes to ETX101.²

The comparison for development relies on an outside study of untreated children rather than a matched group inside the trial.² The groups at each dose are small, from 3 to 9 children, so a few children can move the median a lot.² Neurologist Joseph Sullivan, commenting on the earlier data, said longer-term results for the highest dose were still emerging at that time.² The results have been presented at conferences; the sources do not describe a peer-reviewed paper.

Who is behind it

Encoded Therapeutics makes ETX101 and sponsors its trials.³ The results come from the company’s own presentations, and the comments on how meaningful they are come from its chief medical officer.¹² The sources do not describe outside funding.

How it fits the field

Dravet syndrome affects around one in 20,000 births in the U.S.¹ Most cases are caused by a fault in a gene called SCN1A. This gene holds the recipe for NaV1.1, a protein that forms a channel letting sodium into nerve cells and helps them send signals.¹ There are approved medicines to control seizures, but no gene-based treatment is approved to address the cause.¹

ETX101 uses a harmless virus, called an adeno-associated virus or AAV, to carry its instructions into cells.¹ Rather than replacing or editing the faulty gene, it delivers instructions for an engineered protein that turns up SCN1A activity, aiming to raise NaV1.1 levels. It is designed to do this mainly in inhibitory neurons, the nerve cells that calm brain activity.¹

Another gene-targeted approach, zorevunersen from Stoke Therapeutics and Biogen, also aims to raise NaV1.1. It uses repeated doses of short genetic molecules called antisense oligonucleotides instead of a single dose. It has also reported encouraging seizure and development results and is in Phase 3 testing, the last big stage before a drug can be approved.¹

What to watch next

Inside Precision Medicine reported that Encoded is now testing ETX101 in a larger Phase 2 trial.¹ One of the trials in the program, ENDEAVOR, is listed on the U.S. trial registry as recruiting. It began in 2024 and has three parts. Parts 1A and 1B are open-label, with Part 1A testing rising doses. Part 2, for children aged 6 months to under 4 years, is randomized and double-blind, and compares treated children with children who get a sham procedure and receive the treatment later.³ The registry lists an estimated 113 participants across all parts and a primary completion date of June 2028.³ Its main measure is the change in monthly seizure counts from week 5 to week 52.³ NeurologyLive described ENDEAVOR Part 2 as the pivotal study, the one meant to support a decision on approval.²

The key questions are whether the seizure drops hold up against the sham group, whether the development gains last, and what happens with liver and blood effects as more children are treated.