VTX-801 / Vivet Therapeutics, Pfizer - LARVOL DELTA

From Radiocopper to Cold Copper: Mechanistic Modeling and Simulation to Define Clinical Response Criteria and Biomarkers for VTX-801 in Wilson Disease. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "This model provides a robust quantitative framework to assess copper-related biomarkers in WD and their response to treatment in silico. Trial Registration: EudraCT number: 2019-001157-13."

Biomarker • Journal • Gene Therapies • Genetic Disorders • Metabolic Disorders • Movement Disorders • ATP7B

INTERIM RESULTS: OF THE INTERNATIONAL PHASE I/II GATEWAY GENE THERAPY TRIAL WITH VTX-801 CONDUCTED IN ADULT PATIENTS WITH WILSON DISEASE (AASLD 2025) - P1/2 | "Delivery of ATP7B is possible in human liver using AAV. VTX 801 transduction was successful, however changes in Cu parameters were subtherapeutic. Further study is needed to understand factors affecting the degree of functional transgene expression and its ability to increase biliary copper excretion and Cp levels in humans."

Clinical • Gene therapy • P1/2 data • Gene Therapies • Genetic Disorders • Hepatology • Metabolic Disorders • Movement Disorders • ATP7B

Collaborating Across Borders to Advance Patient Care (ASGCT 2025) - P1/2 | "It evaluates VTX-801 in adult patients with Wilson's Disease (NCT04537377)...The second case focuses on the development of varnimcabtagene autoleucel (Var-Cel) , a CAR-T cell therapy initially created within an academic hospital. Var-Cel is designed to treat certain types of relapsed or refractory B-cell malignancies, such as acute lymphoblastic leukemia and non-Hodgkin lymphoma. This groundbreaking, hospital-originated CAR-T therapy is now reaching patients at a fraction of the traditional cost through a national network, with international expansion already underway."

Clinical • Acute Lymphocytic Leukemia • Genetic Disorders • Hematological Malignancies • Hepatology • Leukemia • Lymphoma • Metabolic Disorders • Movement Disorders • Non-Hodgkin’s Lymphoma • Oncology • ATP7B

GATEWAY: A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease (clinicaltrials.gov) - P1/2 | N=4 | Active, not recruiting | Sponsor: Vivet Therapeutics SAS | Recruiting ➔ Active, not recruiting | N=16 ➔ 4 | Trial completion date: Mar 2029 ➔ Jun 2029

Enrollment change • Enrollment closed • Trial completion date • Genetic Disorders • Hepatology • Metabolic Disorders • Movement Disorders

Interim safety results of the ongoing international phase I/II GATEWAY gene therapy trial with VTX-801 conducted in adult patients with Wilson disease (EASL-ILC 2024) - P1/2 | "Treatment of patients of the GATEWAY Cohort 1 (low dose) has been completed. No serious adverse events have been reported. Follow-up of treated patients and enrolment of Cohort 2 (intermediate dose) are underway."

Clinical • Gene therapy • P1/2 data • Gene Therapies • Genetic Disorders • Hepatology • Metabolic Disorders • Movement Disorders • Pain • ATP7B

GATEWAY: A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease (clinicaltrials.gov) - P1/2 | N=16 | Recruiting | Sponsor: Vivet Therapeutics SAS | Trial primary completion date: Mar 2024 ➔ Mar 2025

Trial primary completion date • Genetic Disorders • Hepatology • Metabolic Disorders • Movement Disorders

Therapeutic Efficacy of the Combination of Long-Term Penicillamine Treatment with a Single Administration of VTX-801 in Wilson's Disease Mice (ASGCT 2023) - "Current medical management relies on life-long oral treatment with copper chelators such as D-penicillamine (DPA) or zinc salts. Altogether these results indicate that treatment with a copper chelator contributes to stabilization of liver disease progression in WD mice. DPA treatment significantly improved the therapeutic efficacy of VTX-801 when administered at 20 weeks of age resulting in full restoration of copper metabolism in the absence of adverse events."

Preclinical • Fibrosis • Genetic Disorders • Hematological Disorders • Hepatology • Immunology • Inflammation • Metabolic Disorders • Movement Disorders • Psychiatry • Rare Diseases • ATP7B

Therapeutic Efficacy of VTX-801 in Advanced Stage of Wilson's Disease in Mice (ASGCT 2023) - "Epub 2019 Mar 20. PMID: 30706949."

Metastases • Preclinical • Fibrosis • Genetic Disorders • Hematological Disorders • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Movement Disorders • Psychiatry • Rare Diseases • ATP7B

GATEWAY: A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease (clinicaltrials.gov) - P1/2 | N=16 | Recruiting | Sponsor: Vivet Therapeutics SAS | Trial completion date: Jul 2027 ➔ Mar 2029 | Trial primary completion date: Jul 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Genetic Disorders • Hepatology • Metabolic Disorders • Movement Disorders

High value of Cu as a tool to evaluate the restoration of physiological copper excretion after gene therapy in Wilson's disease. (PubMed, Mol Ther Methods Clin Dev) - "VTX-801 treatment in WD mice resulted in a significant reduction of hepatic Cu accumulation, the restoration of fecal Cu excretion, and the correction of Cu BK. This study showed that VTX-801 restores physiological copper metabolism in WD mice, confirming the mechanism of action of VTX-801, and demonstrated the translational potential of [Cu]CuCl-PET to explore VTX-801 pharmacodynamics in a minimally invasive and sensitive manner in WD patients."

Journal • Gene Therapies • Genetic Disorders • Hepatology • Metabolic Disorders • Movement Disorders • ATP7B

Safety and Biodistribution of VTX-801, an AAV3B Gene Therapy Vector, in Healthy Cynomolgus Monkeys (ASGCT 2022) - "CONCLUSION This study of a single intravenous administration of VTX-801 in juvenile cynomolgus monkeys demonstrated safety of the doses evaluated with no toxicity, an excellent liver tropism with limited off-target biodistribution, no immune response, and sustained expression of the gene therapy product in vector-treated animals. This study has supported the clinical development of VTX-801 for a first-in-human clinical trial in Wilson’s patients (GATEWAY)."

Clinical • Cardiovascular • Gene Therapies • Hematological Disorders • Hepatology • Metabolic Disorders • Movement Disorders

GATEWAY: A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease (clinicaltrials.gov) - P1/2; N=16; Recruiting; Sponsor: Vivet Therapeutics SAS; Initiation date: Apr 2021 ➔ Aug 2021

Clinical • Trial initiation date • Genetic Disorders • Hepatology • Metabolic Disorders • Movement Disorders • CP