Abstract
Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injectedinto the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction(LVEF) 30%-50% who were undergoing elective coronaryartery bypass surgery. Thirty epicardial injections of AZD8601 (total 3mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6months. There were nodeaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions,orarrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-typenatriuretic peptide levels, but the study is limited insize, and significant efficacy conclusions are not possiblefrom the dataset. Naked mRNA without lipid encapsulationmay provide a safe delivery platform for introducinggenetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool.
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