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

Sodium Channel Blocker Tolerance as a Metric for Disease Modification in Dravet Syndrome. (PubMed, Ann Child Neurol Soc) - No abstract available

Journal • CNS Disorders • Epilepsy

Antiseizure Medications in Development: Novel Mechanisms, Precision Therapy, and the Move Towards Disease Modification. (PubMed, Curr Issues Mol Biol) - "Functional-state-selective sodium channel modulation has emerged as a leading conceptual advance supported by converging mechanistic and early clinical evidence, exemplified by relutrigine (PRAX-562), a preferential persistent-current inhibitor for which a regulatory decision is pending in SCN2A/SCN8A-DEEs, and vormatrigine (PRAX-628), whose large open-label effect was not reproduced in a controlled (blinded) trial...Parallel advances include the selective Kv7 opener azetukalner; the dual-mechanism benchmark cenobamate; cholesterol-24-hydroxylase inhibition (soticlestat); selective serotonergic agonism (bexicaserin); glutamatergic precision agents (radiprodil); subtype-selective GABAA modulators (darigabat, ganaxolone); and gene-directed therapies (zorevunersen, elsunersen)... The pipeline reflects an ongoing shift from broad symptomatic agents toward mechanism-led, genotype-matched, and potentially disease-modifying treatments. This shift is tempered by a persistent..."

Journal • Review • CNS Disorders • Epilepsy • SCN8A

Progress report on new epilepsy treatments: A summary of the Eighteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVIII). II. Treatments in more advanced clinical development. (PubMed, Epilepsia) - "The treatments reviewed include bexicaserin, a selective 5-hydroxytryptamine (5-HT, serotonin) type 2C (5-HT2C) receptor superagonist investigated as a treatment for developmental and epileptic encephalopathies (DEEs); BMB-101, a selective 5-HT2C receptor agonist investigated for the treatment of absence seizures and DEEs; elsunersen, an antisense oligonucleotide designed for the treatment of early-onset SCN2A-DEE; EPX-100 (clemizole hydrochloride), an antihistamine endowed with agonist activity at 5-HT2A and 5-HT2B receptors, repurposed as a treatment for DEEs; ES-481, an antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors containing the transmembrane AMPA receptor regulatory protein γ8 (TARP-γ8), under investigation for the treatment of drug-resistant epilepsy; ETX-101, a gene therapy in development for the treatment of SCN1A-positive Dravet syndrome; PrevEp-006 (intranasal seletracetam), a synaptic vesicle glycoprotein 2A..."

Journal • Absence Seizure Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Psychiatry • GRIN2B • NAV1 • SCN8A

Stoke Therapeutics Announces Completion of Enrollment of 162 Patients Into the Phase 3 EMPEROR Study of Zorevunersen, an Investigational Medicine for the Treatment of Dravet Syndrome (Businesswire) - “Company plans to initiate a rolling U.S. NDA submission to the FDA in the first quarter of 2027…Phase 3 data readout anticipated in the third quarter of 2027 to complete the rolling U.S. NDA submission in the second half of 2027.”

FDA filing • P3 data • Genetic Disorders

Zorevunersen in Children and Adolescents with Dravet Syndrome. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • CNS Disorders • Epilepsy

Zorevunersen in Children and Adolescents with Dravet Syndrome. (PubMed, N Engl J Med) - No abstract available

Journal • CNS Disorders • Epilepsy

At the forefront of gene-based therapies in dravet syndrome. (PubMed, Expert Opin Emerg Drugs) - "Clinically, the ASO STK-001 trial showed favorable safety, pharmacodynamic activity, and durable seizure reduction in Phase 1/2a and open-label extension trials, alongside improvements in adaptive behavior and cognition...Optimization of dosing regimens, durability, and combinatorial approaches targeting parallel molecular pathways will be critical to realize precision gene therapy for DS. Viral gene therapy approaches constitute a promising therapeutic platform, but comprehensive validation will be essential to ascertain their immunogenic safety and demonstrate clinical efficacy."

Journal • Review • CNS Disorders • Epilepsy • Gene Therapies • SCN8A

Enhanced splicing modulation by NMA-modified antisense oligonucleotides. (PubMed, Nucleic Acids Res) - "Nusinersen (Spinraza™) has revolutionized the treatment of spinal muscular atrophy. An NMA-modified SSO is 3.5 -fold more potent than STK-001, a MOE-modified SSO currently in clinical trials. Our data establish the NMA chemistry as a broadly applicable ribose modification that markedly improves the pharmacological profile of SSOs, supporting its development as a next-generation platform for splicing modulation therapies."

Journal • CNS Disorders • Epilepsy • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

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) - P1/2, P2 | "These findings support the potential of zorevunersen as a disease-modifying therapy and warrant its further evaluation in the ongoing Phase 3 study. Funding: Stoke Therapeutics Encore: This abstract was previously presented in full at the 21st Annual Meeting of the Oligonucleotide Therapeutics Society (OTS); October 19-22, 2025; Budapest, Hungary."

Clinical • HEOR • CNS Disorders • Epilepsy • Ventriculomegaly • 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 | "Increased cerebrospinal fluid protein was the most common treatment-related adverse event in the OLEs (44.0%, n=33/75), with no associated clinical manifestations observed. Conclusions 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 | "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

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

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