For decades, Dravet syndrome treatment meant managing seizures and hoping the medications held. There was no way to address the underlying genetic cause. That is starting to change. Two disease-modifying therapies, zorevunersen (an antisense oligonucleotide) and ETX101 (an AAV9 gene therapy), have both received FDA Breakthrough Therapy designation and are moving into pivotal trials. For families who have been living with Dravet for years, this is the most significant progress since Epidiolex was approved in 2018.
This guide covers where the approved treatments stand today, what the two disease-modifying programs look like, how your child's SCN1A mutation affects eligibility, and what caregivers should know about medication conflicts when considering a clinical trial. All of this is written for the parent sitting at the kitchen table after the kids are in bed, trying to figure out what comes next.
The 3 FDA-Approved Dravet Medications
Before getting into the pipeline, here is where the approved treatments stand. Three medications have FDA approval specifically for Dravet syndrome, and they represent real progress compared to where things were ten years ago.
Epidiolex (Cannabidiol)
Epidiolex was approved in June 2018 as the first CBD-based medication cleared by the FDA. It is indicated for seizures associated with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex in patients one year of age and older. In Dravet-specific trials, it significantly reduced convulsive seizure frequency compared to placebo. It remains one of the most commonly prescribed Dravet treatments.
Fintepla ([Fenfluramine](/drugs/fenfluramine))
Fintepla was approved in June 2020 for Dravet patients two years and older. It works as a serotonin releasing agent and has shown substantial seizure reduction in clinical trials. Because fenfluramine can cause valvular heart disease and pulmonary arterial hypertension (a boxed warning on the label, with cases reported since the drug came on the market), Fintepla is only available through a restricted REMS program that requires echocardiogram monitoring before, during, and after treatment. Long-term safety and effectiveness data published in Epilepsia in 2025 have supported its continued use.
Diacomit ([Stiripentol](/drugs/stiripentol))
Stiripentol was approved in August 2018 and its age range was expanded in July 2022 to include patients as young as six months who weigh at least 7 kg. It is the only Dravet treatment approved for infants. Stiripentol is used as an adjunctive therapy with clobazam and is not approved as a standalone treatment.
The Standard of Care Beyond Approved Drugs
Most children with Dravet are on more than one medication. Beyond the three FDA-approved Dravet therapies, the standard of care typically includes valproic acid (Depakote) and clobazam (Onfi) as first-line treatments, with topiramate (Topamax), levetiracetam (Keppra), and clonazepam (Klonopin) used as adjunctive options. Rescue medications like diazepam rectal gel (Diastat) and midazolam nasal spray (Nayzilam) are kept on hand for seizure clusters and prolonged episodes.
[Zorevunersen](/drugs/zorevunersen) (STK-001): Antisense Oligonucleotide Therapy
Zorevunersen is being developed by Stoke Therapeutics in partnership with Biogen, which signed a collaboration agreement in February 2025 covering development and commercialization outside the US, Canada, and Mexico. Biogen announced a $165 million upfront payment to Stoke, which retains full North American rights.
The therapy uses a TANGO (Targeted Augmentation of Nuclear Gene Output) antisense oligonucleotide approach. In simple terms: the SCN1A gene in Dravet patients has one working copy and one broken copy. Zorevunersen targets a natural regulatory mechanism that limits how much protein the working copy produces, effectively turning up the volume on the functional gene. This increases production of the NaV1.1 sodium channel protein that Dravet patients lack.
It is delivered through intrathecal injection (into the spinal fluid, similar to a lumbar puncture) and requires ongoing dosing rather than being a one-time treatment.
Clinical Data So Far
Phase 1/2a results showed a 73.6% median reduction in convulsive seizure frequency at six months after the final loading dose. Follow-up data has shown sustained improvements ranging from 53 to 87% seizure reduction. Beyond seizure frequency, investigators have also documented improvements in cognition, behavior, and quality of life.
Phase 3 EMPEROR Trial
The Phase 3 EMPEROR trial dosed its first patient in August 2025 and enrolled 162 patients aged 2 to 17 years, with enrollment completed in June 2026. The dosing schedule includes two loading doses (70 mg at Day 1 and Week 8) followed by maintenance doses (45 mg at Week 24 and Week 40), with an open-label extension offering 45 mg every four months. Enrollment completion is expected by mid-2026, with topline data expected around mid-2027 and a rolling NDA submission planned for the first half of 2027.
ETX101: AAV9 Gene Therapy
Encoded Therapeutics is developing ETX101, a one-time AAV9-based gene regulation therapy. Unlike zorevunersen, which requires ongoing intrathecal injections, ETX101 is designed as a single intracerebroventricular (ICV) injection delivered directly into the brain's ventricles. The therapy targets SCN1A expression specifically in GABAergic inhibitory interneurons, the cell type most affected in Dravet syndrome.
Clinical Data So Far
The Phase 1/2 POLARIS program has treated participants across 4 dose levels. At the third dose level, investigators reported a median 78% reduction in monthly countable seizure frequency in the first 3 patients followed for 7 months (Encoded, December 2025). Neurodevelopmental improvements have been observed across the first three dose levels. Fourth dose level data were presented in May and September 2026, and the pivotal ENDEAVOR part dosed its first patient on May 6, 2026.
The safety profile has been encouraging. The most common treatment-related side effects were transaminase elevations (a known class effect of AAV gene therapies), which were clinically asymptomatic and resolved in all participants. No treatment-related serious adverse events have been reported.
The FDA granted Breakthrough Therapy designation in January 2026, along with RMAT (Regenerative Medicine Advanced Therapy), Fast Track, Orphan Drug, and Rare Pediatric Disease designations. Encoded announced FDA alignment on pivotal study design in March 2026 and has initiated the pivotal trial, with a BLA submission planned.
Age Ranges for ETX101 Trials
The POLARIS program includes three open-label trials with different age windows. ENDEAVOR (US, NCT05419492) has 3 parts: the first enrolled infants 6 months to under 3 years and is complete, an open-label part now enrolls children 4 to under 18 years, and the pivotal part enrolls 6 months to under 4 years at US, UK and Australian sites. EXPEDITION (UK) enrolls 6 months to under 4 years and WAYFINDER (Australia) 6 months to under 7 years. Zorevunersen's EMPEROR trial accepted patients 2 to 17, but it finished enrolling in June 2026 and is no longer taking new patients outside China. For families with older children, the ENDEAVOR open-label part for ages 4 to 17 is the disease-modifying trial currently open in the United States.
Zorevunersen vs. ETX101: How They Compare
Both therapies target the same underlying problem (insufficient NaV1.1 protein from SCN1A loss-of-function mutations) but take fundamentally different approaches.
Zorevunersen is an antisense oligonucleotide that boosts production from the existing working gene copy. It requires ongoing intrathecal injections every four months. The Phase 3 EMPEROR trial enrolls children aged 2 to 17. ETX101 is a one-time AAV9 gene therapy delivered directly into the brain. The POLARIS trials enroll children as young as 6 months; the pivotal part goes up to age 4 and one open-label part takes ages 4 to 17.
For families deciding between the two, the key practical differences are: age eligibility (ETX101 skews younger, zorevunersen covers a wider range), dosing commitment (one-time vs. ongoing), delivery method (ICV injection vs. intrathecal), and the fact that ETX101 is a one-time AAV gene therapy, which trials of later gene therapies may exclude. Both require confirmed SCN1A mutations.
Other Therapies in the Dravet Pipeline
EPX-100 (Clemizole) by Harmony Biosciences
EPX-100 is a serotonin 5-HT2 receptor modulator in a Phase 3 trial called ARGUS. Harmony Biosciences reported that open-label extension data from December 2025 showed approximately 50% median seizure reduction in 18 participants with at least six months of exposure. An interim report found that all 24 patients who had completed the 16-week double-blind phase went on to the extension, and topline data is expected in 2026.
Lorcaserin by Eisai
Lorcaserin is a selective 5-HT2C serotonin receptor agonist that was tested in a Phase 3 trial called MOMENTUM 1 (NCT04572243). It was designed to target serotonin pathways with less cardiac risk than fenfluramine. Eisai stopped the trial in 2024 for business reasons after enrolling 22 patients, and results posted in 2025 showed a median 78.9% drop in convulsive seizures on lorcaserin versus an 18.8% rise on placebo, 10 patients per group. Lorcaserin was withdrawn from the US market as a weight-loss drug in 2020, and no Dravet program is active.
Gene Editing Research (Preclinical)
Several groups are exploring CRISPR and other gene editing approaches for Dravet, but none have reached clinical trials. The challenge is that over 1,800 distinct SCN1A mutations have been identified, making a one-size-fits-all gene editing strategy difficult. Researchers at the Allen Institute and Seattle Children's Research Institute have published encouraging preclinical data for a different approach, a two-vector gene replacement driven by a cell-type-specific enhancer, showing long-term seizure recovery in mouse models, but human trials are likely years away.
Does Your Child's SCN1A Mutation Affect Trial Eligibility?
Yes. Both zorevunersen and ETX101 require a confirmed pathogenic SCN1A mutation for enrollment. The specific mutation type matters beyond just having a confirmed diagnosis.
Over 1,800 distinct SCN1A mutations have been identified. The most common mutation types include missense mutations (approximately 46%), frameshift mutations (approximately 27%), nonsense mutations (approximately 13%), and splice site mutations (approximately 11%). Approximately 90% of all Dravet-causing SCN1A mutations arise de novo.
One important distinction: gain-of-function SCN1A variants, which cause a different developmental and epileptic encephalopathy rather than Dravet syndrome, are typically excluded from Dravet trials because the disease mechanism is different. Zorevunersen works by boosting NaV1.1 production from the working gene copy. If the problem is a gain-of-function mutation rather than a loss-of-function one, boosting production would not help and could be harmful.
Medication Conflicts and Trial Eligibility
This is one of the most practical questions caregivers face. Most Dravet trials allow participants to continue their current anti-seizure medications as long as the regimen has been stable, typically for several weeks before enrollment; EMPEROR required stability across an 8-week baseline.
Trial Friend's Dravet syndrome page includes a medication conflict checker that scans each active trial's exclusion criteria against three categories of Dravet medications: FDA-approved treatments (Epidiolex, Fintepla, Diacomit), first-line and adjunctive medications (Depakote, Onfi, Topamax, Keppra, Klonopin), and contraindicated sodium channel blockers (Tegretol, Lamictal, Dilantin, Trileptal).
The sodium channel blocker category is unique to Dravet. Unlike most epilepsies where these drugs are standard treatments, in Dravet they are known to worsen seizures because they further suppress the already-impaired inhibitory interneurons. If your child is on a sodium channel blocker, likely because the Dravet diagnosis came after the medication was started, you should discuss this with your neurologist regardless of whether you are considering a clinical trial.
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Questions to Ask Your Child's Neurologist
If you are considering a clinical trial for your child, here are questions that can help guide the conversation:
Does my child's specific SCN1A mutation type (truncating, missense, splice site) affect which trials she qualifies for? Can she participate while continuing her current seizure medications? What is the difference between the antisense oligonucleotide approach (zorevunersen) and the gene therapy approach (ETX101), and is one a better fit for her age and situation? Is she on any sodium channel blockers that should be discontinued regardless of trial participation? Are there age windows we should be aware of, given that the ETX101 pivotal trial caps at age 4 and the open-label part runs to 17? How would trial participation affect her current therapy schedule and seizure management plan?
Where Things Stand in April 2026
Dravet treatment is moving faster than it ever has. Three FDA-approved medications provide a foundation of seizure management that did not exist before 2018. Two disease-modifying therapies are in pivotal trials, with both backed by FDA Breakthrough Therapy designation and significant pharma investment (Biogen's $165 million upfront for zorevunersen alone). Additional serotonin-targeting and gene editing approaches are in the pipeline behind them.
For caregivers, the practical takeaways are: confirm your child's SCN1A mutation through genetic testing if you have not already; know what medications your child is on and whether any are sodium channel blockers that should be reconsidered; understand that age affects eligibility (the ETX101 pivotal trial takes children under 4, an ETX101 open-label part takes ages 4 to 17, and zorevunersen's EMPEROR trial has finished enrolling); and use the Dravet Syndrome Foundation as a resource for tracking trial opportunities and connecting with other families.
“We spent years just reacting to seizures. Now there are actual options to talk about at the next neurology appointment. That feels different.”
A Dravet caregiver
You can explore all active Dravet syndrome clinical trials on Trial Friend, including eligibility criteria in plain English, medication conflict checking, and SCN1A genetic testing resources.