AZD8601 / Moderna - LARVOL DELTA

EPICCURE: AZD8601 Study in CABG Patients (clinicaltrials.gov) - P2 | N=11 | Completed | Sponsor: AstraZeneca | Phase classification: P2a ➔ P2

Phase classification • Cardiovascular • Heart Failure

Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting. (PubMed, Mol Ther) - P2a | "We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart...Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores and N-terminal pro-B-type natriuretic peptide levels but the study is very limited in size and significant efficacy conclusions are not possible from the data set. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool."

Clinical • Journal • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Infectious Disease • VEGFA

"if you drop AZD8601 after testing it on pigs and making us understand you are so confident then medicine is just luck, no science and you are just lucky" (@10_dcar)

"ツイッターを通じて、モデルナ社はアストラゼネカ社と協力し、将来的に同じくmRNAベースの心血管系疾患治療用ワクチンを提供することを発表した。「心不全のような生命を脅かす循環器疾患をmRNAで治療できるとしたら？VEGF-Aをコード化したmRNA治療薬（AZD8601）について、@AstraZeneca社と共同で、" (@ROGoUfwiIZyqwW1)

VEGFA

[VIRTUAL] mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Results of the Phase 2a EPICCURE Clinical Trial (AHA 2021) - P2a | "EPICCURE is a randomized, double-blind, placebo-controlled study of VEGF-A mRNA (AZD8601) in patients undergoing coronary artery bypass surgery and with moderately decreased left ventricular function (ClinicalTrials.gov: NCT03370887)...Data analysis of the recently terminated phase 2a study EPICCURE is currently ongoing. Safety and tolerability data, exploratory efficacy read-outs, such as cardiac function, cardiac biomarkers, and patient reported outcomes will be presented at the annual meeting."

Clinical • P2a data • VEGFA

AZD8601 Study in CABG Patients (clinicaltrials.gov) - P2a; N=11; Completed; Sponsor: AstraZeneca; Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Heart Failure

Mathematical Model Predicts that Acceleration of Diabetic Wound Healing is Dependent on Spatial Distribution of VEGF-A mRNA (AZD8601). (PubMed, Cell Mol Bioeng) - "These findings highlight the critical need to consider the location of drug delivery and diffusivity of the drug, parameters not typically explored in pre-clinical experiments, when designing and testing drugs for treating diabetic wounds. The online version contains supplementary material available at 10.1007/s12195-021-00678-9."

Journal • Diabetes • Metabolic Disorders • VEGFA

AZD8601 Study in CABG Patients (clinicaltrials.gov) - P2a; N=11; Active, not recruiting; Sponsor: AstraZeneca; Recruiting ➔ Active, not recruiting; N=24 ➔ 11

Enrollment change • Enrollment closed • Cardiovascular • Heart Failure

AZD8601 Study in CABG Patients (clinicaltrials.gov) - P2a; N=24; Recruiting; Sponsor: AstraZeneca; Trial completion date: Mar 2022 ➔ Jan 2023; Trial primary completion date: Mar 2022 ➔ Jan 2023

Clinical • Trial completion date • Trial primary completion date • Cardiovascular • Heart Failure

Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial. (PubMed, Mol Ther Methods Clin Dev) - P2a | "AZD8601 is VEGF-A mRNA formulated in biocompatible citrate-buffered saline and optimized for high-efficiency VEGF-A expression with minimal innate immune response...Improvement in regional and global myocardial blood flow quantified with O-water PET is an exploratory efficacy outcome, together with echocardiographic, clinical, functional, and biomarker measures. EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887)."

Clinical • Journal • P2a data • Cardiovascular • Coronary Artery Disease • Reperfusion Injury • VEGFA

Model-based analysis reveals a sustained and dose-dependent acceleration of wound healing by VEGF-A mRNA (AZD8601). (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Instead, we found that administration of AZD8601 induced a sustained acceleration of wound healing depending on the accumulated dose, with an ED of 92 µg. Simulations with this model showed that a single dose of 200 µg AZD8601 can reduce the time to reach 50% wound healing by up to 5 days."

Journal • Diabetes • VEGFA

AZD8601 Study in CABG Patients (clinicaltrials.gov) - P2a; N=33; Recruiting; Sponsor: AstraZeneca; Trial completion date: Jan 2021 ➔ Mar 2022; Trial primary completion date: Jan 2021 ➔ Mar 2022

Clinical • Trial completion date • Trial primary completion date

Modified VEGF-A mRNA induces sustained multifaceted microvascular response and accelerates diabetic wound healing. (PubMed, Sci Rep) - "Moreover, we evaluate the bioactivity of AZD8601 in a mouse model of diabetic wound healing in vivo. Using a boron nanoparticle-based tissue oxygen sensor, we show that sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing."

Journal

AZD8601 Study in CABG Patients (clinicaltrials.gov) - P2a; N=33; Recruiting; Sponsor: AstraZeneca; Trial completion date: Jul 2020 ➔ Jan 2021; Trial primary completion date: Jul 2020 ➔ Jan 2021

Clinical • Trial completion date • Trial primary completion date