zorevunersen (STK-001) / Stoke Therap, Biogen - LARVOL DELTA

Zorevunersen demonstrates potential as a disease‑modifying therapy in patients with Dravet syndrome through durable seizure reduction and improvements in cognition, behavior, and quality of life through 36 months in open-label extension studies (ASGCT 2026) - No abstract available

Clinical • HEOR • CNS Disorders • Epilepsy

Zorevunersen in Children and Adolescents with Dravet Syndrome. (PubMed, N Engl J Med) - P1/2, P2 | "The safety profile and initial clinical improvement support the continued development of zorevunersen as a potential disease-modifying treatment for Dravet syndrome. (Supported by Stoke Therapeutics; MONARCH and SWALLOWTAIL ClinicalTrials.gov numbers, NCT04442295 and NCT04740476, respectively; ADMIRAL and LONGWING ISRCTN Registry numbers, ISRCTN99651026 and ISRCTN12811235, respectively.)."

Journal • CNS Disorders • Cognitive Disorders • Epilepsy • NAV1

Zorevunersen Demonstrates Potential as a Disease-modifying Therapy in Patients with Dravet Syndrome Through Durable Seizure Reduction and Improvements in Cognition, Behavior, and Quality of Life Through 36 Months of Treatment in Open-label Extension Studies (AAN 2026) - P1/2, P2 | "Substantial and durable seizure reductions and continuing improvements in cognition, behavior, and QoL support the potential of zorevunersen as a disease-modifying therapy and warrant further evaluation in the ongoing Phase 3 study."

Clinical • HEOR • CNS Disorders • Epilepsy • NAV1

Electrophysiological Improvements in Patients with Dravet Syndrome Following Treatment with Zorevunersen, an Investigational Antisense Oligonucleotide (AAN 2026) - P1/2 | "Dose-dependent changes in δ-power were observed at both timepoints, yet clinical changes emerged 24 weeks after last dose, suggesting δ-power changes may precede and support potential clinical improvements. These findings are consistent with zorevunersen's mechanism and support EEG δ-power as a potential biomarker to capture neurophysiological changes in DS following disease-modifying therapies. Confirmation in a larger study is needed."

Clinical • CNS Disorders • Epilepsy • NAV1

STK-001-DS-301: EMPEROR: A Double-blind Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen (STK-001) in Patients with Dravet Syndrome (clinicaltrialsregister.eu) - P2/3 | N=35 | Not yet recruiting | Sponsor: Stoke Therapeutics Inc. | N=51 ➔ 35

Enrollment change • CNS Disorders • Epilepsy

STK-001-DS-301: EMPEROR: A Double-blind Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen (STK-001) in Patients with Dravet Syndrome (clinicaltrialsregister.eu) - P2/3 | N=51 | Not yet recruiting | Sponsor: Stoke Therapeutics Inc.

New P2/3 trial • CNS Disorders • Epilepsy

Ameliorating Seizures in Dravet Syndrome: A Review of Newly Approved and Investigational Drugs, RNA and Gene-Based Therapies. (PubMed, CNS Drugs) - "Recent therapeutic developments include the approval of new antiseizure medications such as fenfluramine and pharmaceutical-grade cannabidiol, which have demonstrated efficacy and tolerability in randomised placebo-controlled trials...Antisense oligonucleotides (e.g., STK-001) aim to restore SCN1A expression, while emerging gene therapy approaches, including engineered AAV vectors (e.g., ETX101) and CRISPR-mediated transcriptional activation, seek to directly modify disease biology...Future directions include defining the most effective genetic therapies to improve outcomes, and ideally cure, all features of DS; optimal timing to deliver interventions as well as benefits derived from administration at later ages; ideal combinations of therapies; comparison of outcomes of targeted therapies with natural history studies and biomarker development. Together, these advances signal a paradigm shift in epilepsy management from symptomatic treatment to precision medicine for..."

Journal • Review • CNS Disorders • Epilepsy • Gene Therapies • NAV1

A Double-blind Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen in Patients With Dravet Syndrome (clinicaltrials.gov) - P3 | N=170 | Recruiting | Sponsor: Stoke Therapeutics, Inc | Trial completion date: Aug 2027 ➔ Oct 2028

Trial completion date • CNS Disorders • Epilepsy

From Symptomatic Therapies to Disease-Modifying Approaches for Neuronal Sodium Channel Disorders. (PubMed, Int J Mol Sci) - "Additionally, pharmacological agents such as fenfluramine, stiripentol, and cannabidiol, although not acting directly on sodium channels, represent recognized therapeutic options for SCN1A-related Dravet syndrome. This review summarizes recent advances in approved and investigational treatments for sodium channel-related neurological disorders, highlighting the transition from symptomatic to precision therapies."

Journal • Review • CNS Disorders • Epilepsy • Gene Therapies

Electrophysiological Improvements in Patients with Dravet Syndrome Following Treatment with Zorevunersen, an Investigational Antisense Oligonucleotide (AES 2025) - P1/2 | "Zorevunersen was associated with dose-dependent improvements in the elevated δ-power, a characteristic of DS. Changes in EEG δ-power were associated with seizure reduction and improvement in some relevant clinical domains at 24 weeks after last dose. Although EEG changes were seen as early as 12 weeks after treatment, clinical changes manifested at 24 weeks, indicating that δ-power changes may precede and support potential clinical improvements."

Clinical • Late-breaking abstract • CNS Disorders • Epilepsy • NAV1

Zorevunersen Continues to Demonstrate Potential as a Disease-modifying Therapy in Long-term Open-label Extension Studies of Patients with Dravet Syndrome (AES 2025) - P1/2, P2 | "Patients treated with zorevunersen experienced substantial and durable seizure reductions along with continuing improvements in cognition, behavior and overall functioning despite already receiving the best available ASMs. These findings support the potential of zorevunersen as a disease-modifying therapy and warrant its further evaluation in the ongoing Phase 3 study."

Clinical • CNS Disorders • Epilepsy • Ventriculomegaly • NAV1

Zorevunersen for Dravet Syndrome: Understanding the Safety Profile of CSF Protein Elevations (AES 2025) - P1/2 | "Our data support the hypothesis that albumin penetration through the blood-brain and blood-CSF barriers is the most likely pathophysiologic factor accounting for the transient elevation in CSF protein. These data coincide with reports of CSF alterations triggered by other ASOs requiring intrathecal administration with no new side effects identified. Additionally, the pattern of CSF protein elevation appeared consistent with cumulative dose effect."

Clinical • Late-breaking abstract • CNS Disorders • Epilepsy • Hematological Disorders • Ventriculomegaly

Spectral Electroencephalogram Abnormalities Across Development in Patients with Dravet Syndrome (AES 2025) - P1/2 | "Our findings demonstrate that EEG δ-power is useful in distinguishing between children with DS and neurotypical individuals. Although children with DS showed decreasing δ-power with age, similarly to neurotypical individuals [3], they demonstrated a stable elevation across development (ages 2–18 years). This persistent δ-band abnormality may reflect DS-related pathophysiology, warranting its further exploration as a potential biomarker to assess disease modification induced by novel therapies such as zorevunersen."

Clinical • Late-breaking abstract • CNS Disorders • Epilepsy

Zorevunersen Demonstrates Disease-modifying Potential in Patients with Dravet Syndrome with Increases in Seizure-free Days, Improvements in Quality of Life, and Benefits in Overall Functioning (AES 2025) - P1/2, P2 | "Treatment with zorevunersen resulted in durable seizure reduction, increased seizure-free days, and improvements in QoL and overall functioning in patients with DS. These findings support the potential of zorevunersen as a disease-modifying therapy and are further evaluated in the ongoing Phase 3 study."

Clinical • HEOR • CNS Disorders • Epilepsy • Ventriculomegaly • NAV1

Zorevunersen Demonstrates Substantial Reduction in Seizure Frequency with or Without the Use of Fenfluramine in Patients with Dravet Syndrome (AES 2025) - P1/2, P2 | "Zorevunersen demonstrated substantial and durable seizure reduction and continuing improvements in overall functioning independent of FFA use. These findings support zorevunersen's potential as a disease-modifying therapy and will be further examined in its Phase 3 registration study."

Clinical • CNS Disorders • Epilepsy • NAV1

The zorevunersen story: insights from the development of the first potential disease-modifying medicine for Dravet syndrome (ESGCT 2024) - No abstract available

CNS Disorders • Epilepsy

SWALLOWTAIL: An Open-Label Extension Study of STK-001 for Patients With Dravet Syndrome (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Stoke Therapeutics, Inc | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Mar 2027 ➔ Mar 2029 | Trial primary completion date: Feb 2026 ➔ Mar 2029

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Voltage-gated sodium channels in the nervous system: Molecular physiology to therapeutic interventions. (PubMed, Neural Regen Res) - "It analyzes two major categories of conventional sodium channel blockers and their applications: antiepileptic drugs (such as carbamazepine, lamotrigine, and phenytoin) and antiarrhythmic drugs (such as lidocaine, flecainide, and quinidine)...Additionally, this review evaluates gabapentin, cannabidiol, and calcium channel blockers with different mechanisms of action...This review also highlights advances in gene therapy for specific diseases, such as STK-001, which promotes effective splicing of the SCN1A gene, and ETX101, which utilizes adeno-associated virus 9 vectors to deliver engineered transcription factors...Furthermore, this review summarizes some innovative therapeutic agents in clinical trials, including PRAX-222 (for SCN2A gain-of-function mutation-related epilepsy), which has received Food and Drug Administration orphan drug designation, and the selective Nav1.6 inhibitor NBI-921352 (for SCN8A-related epilepsy). Collectively, this review comprehensively..."

Journal • Autism Spectrum Disorder • CNS Disorders • Epilepsy • Gene Therapies • Genetic Disorders • Migraine • Ophthalmology • Pain • NAV1 • SCN8A

Biogen and Stoke Therapeutics Announce Presentation of Data from Studies of Zorevunersen, an Investigational Medicine for Dravet syndrome, at the 16th European Paediatric Neurology Society (EPNS) Congress (Biogen Press Release) - "A mixed-effects model for repeated measures (MMRM) analysis was used to evaluate the potential effects of the Phase 3 zorevunersen dosing regimen on patient cognition and behavior at Week 68. The model was developed using clinical data from patients in the Phase 1/2a ADMIRAL study and the LONGWING OLE study. An analysis of patients who received a total cumulative dose consistent with the Phase 3 EMPEROR regimen of two loading doses of 70mg followed by two maintenance doses of 45mg, showed improvements in cognition and behavior. The analysis was performed to inform the design of the Phase 3 EMPEROR study. Baseline covariates for patients followed in the BUTTERFLY natural history study were matched to the selected ADMIRAL patient population. Improvements in patients treated with zorevunersen contrasted with findings from BUTTERFLY."

Clinical data • Epilepsy

A Double-blind Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen in Patients With Dravet Syndrome (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Stoke Therapeutics, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Epilepsy

Current and Emerging Precision Therapies for Developmental and Epileptic Encephalopathies. (PubMed, Pediatr Neurol) - "Targeted approaches for channelopathies include antisense oligonucleotides and gene therapies, such as zorevunersen and ETX101 for SCN1A-related Dravet syndrome, alongside novel small molecules for other ion channel disorders. Advances in targeting neurotransmitter receptor dysfunctions, including γ-aminobutyric acid and glutamate receptor variants, highlight the use of modulators such as gaboxadol, radiprodil, and l-serine, alongside emerging gene therapies...Future directions focus on addressing the challenges in developing and implementing gene-based therapies, integrating systems biology, leveraging artificial intelligence for data analysis, and fostering collaboration among stakeholders. The rapidly advancing field of precision therapeutics for DEEs holds promise to improve outcomes through tailored, equitable, and patient-centered care."

Journal • Review • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Metabolic Disorders • Movement Disorders • XBP1

Stoke Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Updates (Businesswire) - "Phase 3 EMPEROR study of zorevunersen, a first-in-class potential disease-modifying medicine for Dravet syndrome, on track to initiate in 2Q 2025."

Trial status • CNS Disorders • Epilepsy

A Double-blind Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen in Patients with Dravet Syndrome (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: Stoke Therapeutics, Inc

New P3 trial • CNS Disorders • Epilepsy

Biogen and Stoke Therapeutics Enter into Collaboration to Develop and Commercialize Zorevunersen for the Treatment of Dravet Syndrome, a Rare Genetic Epilepsy Associated with Refractory Seizures and Neurodevelopmental Impairments (GlobeNewswire) - "Biogen...and Stoke Therapeutics...announced a collaboration for the development and commercialization of zorevunersen, a potential first-in-class disease modifying medicine in development for the treatment of Dravet syndrome, in all territories outside the United States, Canada, and Mexico. Zorevunersen is an investigational antisense oligonucleotide (ASO) that targets the SCN1A gene, the underlying cause of most cases of Dravet syndrome. Stoke recently announced plans to initiate a global Phase 3 registrational study of zorevunersen (EMPEROR) following successful alignment with regulatory agencies in the United States, Europe, and Japan. The study is on track to initiate in the second quarter of 2025, with a pivotal data readout expected in the second half of 2027, which is anticipated to support global regulatory filings."

Licensing / partnership • New P3 trial • CNS Disorders • Epilepsy

Stoke Therapeutics to Host Webcast to Discuss Successful Global Regulatory Alignment for a Phase 3 Study of Zorevunersen as Potentially the First Disease Modifying Medicine for Dravet Syndrome (Businesswire) - "Stoke Therapeutics...today announced that its management team will host a webcast and conference call for investors and analysts to discuss successful alignment with global regulatory agencies related to a Phase 3 study of zorevunersen as potentially the first disease-modifying medicine for the treatment of Dravet syndrome."

Clinical • CNS Disorders