Phoenix Children’s Joins First Controlled Clinical Trial of Genetic Therapy for Dravet Syndrome
Phoenix Children’s is among 28 clinical sites nationwide participating in EMPEROR, a phase 3 study evaluating zorevunersen, a genetic therapy for Dravet syndrome – one of the most severe developmental and epileptic encephalopathies. EMPEROR is the first controlled clinical trial of this genetic therapy, building on findings from MONARCH, an earlier open-label, proof-of-concept study that first demonstrated the therapy’s potential in 2020.
This investigational study represents an important step forward in precision medicine for pediatric epilepsy, aiming to address the underlying genetic cause rather than solely managing symptoms.
Understanding Dravet Syndrome
Dravet syndrome is a rare, monogenic epilepsy most commonly caused by pathogenic variants in the SCN1A gene, which encodes the Nav1.1 voltage-gated sodium channel. Clinical manifestations typically begin within the first year of life and include:
- Pharmacoresistant seizures
- Developmental delay
- Increased risk of premature mortality, including sudden unexpected death in epilepsy (SUDEP)
The severity of the condition and its well-characterized genetic basis make Dravet syndrome a compelling candidate for gene-based therapeutic approaches.
Why Dravet Is a Target for Gene-Based Therapy
Dravet syndrome occupies a unique position within the landscape of genetic epilepsies.
While many genetic epilepsies are currently under investigation, Dravet’s defined molecular etiology, high unmet clinical need and profound impact on patients and families position it as a priority for therapeutic development.
How the Investigational Therapy Works
This investigational approach does not involve traditional gene replacement. The SCN1A coding sequence exceeds the packaging capacity of commonly used viral vectors, necessitating an alternative strategy.
Instead, the therapy uses antisense oligonucleotides (ASOs) to modulate gene expression. In SCN1A-related Dravet syndrome:
- The condition typically results from haploinsufficiency in an autosomal dominant context.
- Patients retain one intact SCN1A allele, but expression is insufficient to maintain normal neuronal excitability.
The ASO-based therapy is designed to upregulate expression from the functional allele, increasing Nav1.1 protein levels and partially restoring inhibitory interneuron function. This approach enhances endogenous gene output rather than replacing the gene entirely, directly targeting the disorder’s underlying pathophysiology.
Clinical Trial Design and Patient Participation
Phoenix Children’s enrolled eight participants in this year-long clinical trial, drawing patients from Arizona and across the country.
Key elements of the study protocol include:
- Four intrathecal administrations of the ASO
- Delivery via lumbar puncture
- Focus on sustained seizure control, along with enhanced neurocognitive and coordination skills
Participants continue to be closely monitored for safety, tolerability and early signals of clinical impact throughout the study period.
Looking Ahead: A Paradigm Shift in Epilepsy Care
Gene-targeted therapies represent a significant shift in epilepsy treatment – moving beyond symptomatic seizure control toward disease modification at the molecular level.
The study’s primary endpoint is the change from baseline in major motor seizure frequency, with secondary endpoints assessing changes in behavior, cognition, clinical status and health-related quality of life. If successful, this approach has the potential to meaningfully alter the clinical trajectory of Dravet syndrome and may serve as a framework for precision therapies across a broader spectrum of genetic epilepsies.
This phase 3 study is registered at ClinicalTrials.gov under NCT06872125.
Refer a Patient or Request a Consult
Barrow Neurological Institute at Phoenix Children's provides comprehensive evaluation and management for children with Dravet syndrome, SCN1A-related epilepsies and other rare genetic developmental and epileptic encephalopathies – including access to precision-guided care and emerging clinical trials. To refer a patient or request a consultation, call Phoenix Children's Neurology at 602-933-0970.
About the Author
Division Chief, Neurology; Dr. Jerry Cox Endowed Chair in Neurology, Barrow Neurological Institute at Phoenix Children’s
Dr. Wilfong is a nationally recognized leader in pediatric epilepsy and neurogenetic disorders. His work focuses on advancing precision-based therapies and improving outcomes for children with severe and treatment-resistant epilepsies.