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First treatment targeting the genetic root of Dravet syndrome shows dramatic seizure reduction

First treatment targeting the genetic root of Dravet syndrome shows dramatic seizure reduction

New Capabilities

Zorevunersen's NEJM data mark a potential shift from symptom management to disease modification in severe childhood epilepsy

March 5th, 2026: NEJM publishes first disease-modifying evidence for Dravet syndrome

Overview

For nearly five decades, children born with Dravet syndrome—a severe genetic epilepsy that causes hundreds of seizures per month, cognitive decline, and a mortality rate between 15 and 20 percent—had no treatment that addressed the underlying cause. Every available drug, including two approved in the past eight years, could only partially suppress symptoms. On March 5, 2026, the New England Journal of Medicine published the first clinical evidence that a drug can modify the disease itself: zorevunersen, an antisense oligonucleotide that boosts protein production from the healthy copy of the gene responsible for the condition, reduced motor seizures by up to 91 percent in 81 children and sustained improvements in cognition and behavior over three years.

The significance extends beyond Dravet syndrome's roughly 1-in-16,000 affected children. Zorevunersen validates a therapeutic approach—using short RNA molecules to coax a working gene copy into producing more protein—that could apply to hundreds of other conditions caused by loss-of-function mutations in a single gene. A Phase 3 trial of approximately 150 patients is expected to finish enrollment by mid-2026, with results anticipated in mid-2027 that could support a Food and Drug Administration (FDA) submission. If approved, zorevunersen would be the first disease-modifying treatment for any genetic epilepsy.

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Key Indicators

91%
Maximum seizure reduction
Median reduction in convulsive seizure frequency observed in the highest-dose cohort during the open-label extension studies.
81
Patients treated
Children and adolescents ages 2 to 18 who received at least one dose of zorevunersen across Phase 1/2a studies.
3 years
Sustained benefit duration
Duration over which improvements in seizures, cognition, and behavior were maintained in extension studies.
~150
Phase 3 enrollment target
Number of patients in the EMPEROR registrational trial, with enrollment expected to complete in Q2 2026.
1 in 15,700
Incidence rate
Estimated incidence of Dravet syndrome per live births in the United States—more than twice earlier estimates.

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People Involved

Adrian Krainer
Adrian Krainer
Co-founder of Stoke Therapeutics and scientific architect of the TANGO platform
 Isabel Aznarez
Isabel Aznarez
Co-founder of Stoke Therapeutics and co-inventor of the TANGO platform
 Charlotte Dravet
Charlotte Dravet
Retired; the condition bears her name

Organizations Involved

Stoke Therapeutics
Stoke Therapeutics
Biotechnology Company
Developer of zorevunersen; leading the Phase 3 EMPEROR trial

A publicly traded biotechnology company developing antisense oligonucleotide therapies for genetic diseases caused by insufficient protein production.
Biogen
Biogen
Pharmaceutical Company
Co-developer with rights to zorevunersen outside North America

A major neuroscience-focused pharmaceutical company that previously brought the first antisense oligonucleotide therapy for a neurodegenerative disease (Spinraza for spinal muscular atrophy) to market.
U.S. Food and Drug Administration
U.S. Food and Drug Administration
Federal regulatory agency
Granted Breakthrough Therapy Designation to zorevunersen

The U.S. agency responsible for approving new drugs; its Breakthrough Therapy Designation allows accelerated development for drugs treating serious conditions.

Timeline

  1. NEJM publishes first disease-modifying evidence for Dravet syndrome

    Scientific

    The New England Journal of Medicine publishes results from Phase 1/2a and open-label extension studies showing zorevunersen reduced seizures by up to 91 percent in 81 children, with sustained cognitive and behavioral improvements over three years—the first evidence of disease modification in any genetic epilepsy.

  2. Phase 3 EMPEROR trial on track, enrollment nearing completion

    Clinical

    Stoke announces that approximately 60 patients have been randomized and dosed in the Phase 3 EMPEROR trial, with enrollment of 150 patients expected to complete in Q2 2026 and data readout targeted for mid-2027.

  3. Three-year data presented at American Epilepsy Society meeting

    Scientific

    Presentations at the American Epilepsy Society annual meeting show durable improvements in seizures, cognition, and behavior through 36 months of treatment across open-label extension studies.

  4. Data at International Epilepsy Congress support disease modification

    Scientific

    Stoke and Biogen present data at the 36th International Epilepsy Congress showing sustained seizure reduction and cognitive improvements that support zorevunersen's disease-modifying potential.

  5. Biogen pays $165 million to partner on zorevunersen

    Corporate

    Biogen enters a collaboration with Stoke Therapeutics worth up to $550 million for rights to zorevunersen outside North America, covering 30 percent of development costs.

  6. FDA grants Breakthrough Therapy Designation to zorevunersen

    Regulatory

    The FDA designates zorevunersen a Breakthrough Therapy for Dravet syndrome, signaling substantial improvement over existing treatments and enabling accelerated development pathways.

  7. FDA approves fenfluramine as second Dravet treatment

    Regulatory

    Fintepla (fenfluramine) becomes the second FDA-approved treatment for Dravet syndrome seizures, still focused on symptom management rather than the disease mechanism.

  8. Charlotte Figi dies at age 13

    Milestone

    Charlotte Figi, whose story transformed medical cannabis policy in the United States and gave hope to Dravet families, dies of complications from pneumonia at age 13.

  9. FDA approves Epidiolex, first cannabidiol drug for Dravet

    Regulatory

    The FDA approves Epidiolex (cannabidiol) as the first prescription CBD treatment for Dravet syndrome seizures, managing symptoms but not addressing the underlying genetic cause.

  10. Stoke Therapeutics founded to target Dravet's root cause

    Corporate

    Adrian Krainer and Isabel Aznarez launch Stoke Therapeutics with $40 million in funding to develop antisense oligonucleotide therapies using their TANGO platform, beginning with Dravet syndrome.

  11. Charlotte Figi's story popularizes CBD treatment for Dravet

    Milestone

    Five-year-old Charlotte Figi, experiencing 300 seizures per week, begins taking a low-THC cannabis extract that reduces her seizures dramatically. Her story sparks a national conversation about medical cannabis.

  12. SCN1A gene identified as the cause of most Dravet cases

    Discovery

    Researchers discover that mutations in the SCN1A gene, which encodes a sodium channel protein critical for brain function, cause over 90 percent of Dravet syndrome cases.

  13. Charlotte Dravet describes a new epilepsy syndrome in infants

    Discovery

    French epileptologist Charlotte Dravet documents a pattern of severe seizures beginning in the first year of life that resists standard treatments, initially called severe myoclonic epilepsy of infancy.

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1

FDA approves zorevunersen as first disease-modifying treatment for genetic epilepsy

If the Phase 3 EMPEROR trial replicates the seizure reduction and cognitive improvement seen in Phase 1/2a studies, Stoke plans to begin a rolling new drug application to the FDA in the first half of 2027, with potential approval by late 2027 or 2028. The FDA's Breakthrough Therapy Designation and engagement on expedited pathways suggest willingness to move quickly. Approval would establish zorevunersen as the first drug for any genetic epilepsy that addresses the underlying cause rather than suppressing symptoms, and could accelerate regulatory consideration for similar antisense therapies targeting other haploinsufficiency disorders.

Discussed by: Stoke Therapeutics investor communications, NeurologyLive, and analysts tracking Biogen's neuroscience pipeline
Consensus —
2

Phase 3 results disappoint, delaying or ending the path to approval

Open-label studies—where both patients and doctors know the treatment is being given—historically produce more optimistic results than blinded, controlled trials. The EMPEROR study uses a sham comparator (a simulated injection) rather than a true placebo, which should reduce bias, but the smaller patient numbers in rare disease trials leave room for statistical uncertainty. If the Phase 3 data show a less dramatic seizure reduction or if the sham-controlled design narrows the treatment effect, Stoke may need to redesign the trial or negotiate with regulators on alternative endpoints, adding years to the timeline.

Discussed by: Biotech analysts and rare disease research community noting the gap between open-label and controlled trial results
Consensus —
3

Zorevunersen's success catalyzes a wave of gene-regulation therapies for rare diseases

The TANGO platform's approach—boosting protein production from a healthy gene copy using antisense oligonucleotides—is theoretically applicable to any condition caused by haploinsufficiency, where one mutated gene copy leaves the other producing insufficient protein. Stoke is already developing a second compound, STK-002, for autosomal dominant optic atrophy (a genetic cause of blindness). A successful zorevunersen approval would validate the platform approach and could accelerate development of similar therapies for conditions like Rett syndrome, certain forms of autism, and other rare neurological diseases. Biogen's $550 million investment signals confidence in this broader applicability.

Discussed by: Rare disease research organizations, genetic therapy developers, and analysts at firms covering precision medicine
Consensus —
4

Long-term safety concerns emerge with chronic intrathecal dosing

Zorevunersen is delivered via intrathecal injection—directly into the spinal fluid—and must be given repeatedly to maintain its effect. In extension studies, 44 percent of patients experienced cerebrospinal fluid protein elevations, the most common treatment-related adverse event. While these have not caused clinical problems so far, the long-term consequences of chronic CSF protein elevation in developing brains remain unknown. If safety signals emerge with larger numbers or longer follow-up, regulators could impose restrictions that limit the drug's practical impact, similar to the monitoring requirements placed on fenfluramine for its cardiac risks.

Discussed by: Neurologists and safety pharmacologists noting cerebrospinal fluid protein elevations in 44% of extension study patients
Consensus —

Historical Context

Spinraza for spinal muscular atrophy (2016)

December 2016

What Happened

Biogen and Ionis Pharmaceuticals won FDA approval for nusinersen (Spinraza), an antisense oligonucleotide delivered via intrathecal injection to treat spinal muscular atrophy (SMA), a genetic disease that destroys motor neurons in infants and children. In the pivotal ENDEAR trial, 51 percent of treated infants achieved motor milestones versus zero percent in the control group, with a 47 percent reduction in the risk of death or permanent ventilation.

Outcome

Short Term

Spinraza became the first approved treatment for SMA and demonstrated that antisense oligonucleotides delivered to the central nervous system could modify a genetic disease. It generated over $2 billion in annual revenue at peak.

Long Term

Spinraza validated the entire class of intrathecally delivered antisense oligonucleotides for neurological genetic diseases and proved that boosting protein production from a related gene could compensate for a defective one—the same principle underlying zorevunersen.

Why It's Relevant Today

Zorevunersen uses the same drug class (antisense oligonucleotide), the same delivery method (intrathecal injection), and involves the same commercial partner (Biogen) as Spinraza. Adrian Krainer, Stoke's co-founder, contributed to the RNA splicing research that enabled Spinraza. The Dravet program is essentially applying lessons from the SMA success to a different genetic disease.

Charlotte Figi and the medical cannabis movement for epilepsy (2012-2018)

2012-2018

What Happened

Charlotte Figi, a five-year-old with Dravet syndrome experiencing up to 300 seizures per week, began taking a low-THC cannabis extract in 2012 that reduced her seizures to two or three per month. Her story, featured in a 2013 CNN documentary by Sanjay Gupta, transformed the national debate on medical cannabis and led directly to the FDA's 2018 approval of Epidiolex, the first prescription cannabidiol drug.

Outcome

Short Term

Charlotte's story catalyzed medical cannabis legalization across dozens of U.S. states and gave the Dravet community its first moments of public visibility. Epidiolex showed 43 percent of patients achieving a greater than 50 percent seizure reduction.

Long Term

While Epidiolex and fenfluramine improved seizure management, neither addressed the underlying genetic cause. Charlotte Figi died in 2020 at age 13. The gap between symptom management and disease modification underscored the need for therapies like zorevunersen that target the root mechanism.

Why It's Relevant Today

The Dravet community's experience with CBD illustrates both the desperation that drives families toward any available treatment and the limits of symptom management. Zorevunersen's disease-modifying data represent a fundamentally different approach—not suppressing seizures after they start, but addressing the protein deficiency that causes them.

Inotersen and tafamidis for hereditary transthyretin amyloidosis (2018)

2018

What Happened

In 2018, the FDA approved two drugs targeting the same rare genetic disease through different mechanisms: inotersen (an antisense oligonucleotide that reduces production of a misfolded protein) and tafamidis (a small molecule that stabilizes the protein). Both demonstrated disease modification in hereditary transthyretin amyloidosis, a condition where a single gene mutation causes toxic protein buildup that damages the heart and nerves.

Outcome

Short Term

Both approvals validated the principle that targeting a disease's genetic mechanism—rather than its downstream symptoms—could produce durable clinical benefit in rare genetic conditions.

Long Term

The transthyretin amyloidosis approvals helped establish the regulatory and commercial framework for precision genetic medicines, demonstrating that rare disease drugs targeting root causes could command premium pricing and achieve meaningful market adoption despite small patient populations.

Why It's Relevant Today

Like zorevunersen, these drugs showed that modifying gene expression or protein function in a rare genetic disease could yield durable, disease-modifying results. They established the regulatory precedent and commercial viability that companies like Stoke are now building on.

Sources

(10)
+4
The New England Journal of Medicine Biogen Investor Relations ScienceDaily Stoke Therapeutics Investor Relations NeurologyLive Stoke Therapeutics Rare Disease Advisor Dravet Syndrome Foundation Biogen Investor Relations Stoke Therapeutics Investor Relations