Experimental mRNA Injection Safe, Tolerable for Patients With Heart Failure

The injection of mRNA encoding vascular endothelial growth factor (VEGF-A) into the myocardium of patients undergoing elective coronary artery bypass surgery (CABG) was both safe and tolerable in patients with heart failure, according to the results of the phase 2a EPICCURE trial. Referred to as AZD8601, the mRNA injection is intended to assist in repairing heart damage following a heart attack.

“Over one billion heart cells can be lost during a heart attack,” said Mene Pangalos, PhD, executive vice president of BioPharmaceuticals R&D at AstraZeneca, in a press release. “These early results indicate the potential of mRNA therapeutics in stimulating VEGF-A production to provide reparative and disease-modifying options for patients with heart failure and other ischemic vascular diseases.”

According to the investigators, VEGF-A is a paracrine factor important for new blood vessel formation. It has also been demonstrated to stimulate progenitor cell division, descendants of stem cells that, when stimulated, differentiate to create specialized cell types that can contribute to the repair and regeneration of the heart.

The randomized, double-blinded, multi-center, placebo-controlled study observed 11 patients with stable coronary artery disease and moderately decreased left ventricular ejection fraction (LVEF) undergoing CABG surgery. Seven of these patients received AZD8601 treatment and 4 received placebo injections.

The primary endpoint was safety and tolerability, which was met. The investigators also observed trends in 3 exploratory efficacy endpoints: LVEF, NT-proBNP (a biomarker measuring the level of a hormone, which is elevated in patients with heart failure), and functional patient reported outcomes, compared to placebo.

“mRNA is a compelling therapeutic modality because of its ability to act locally and transiently, while driving dose-dependent protein expression,” said Stéphane Bancel, CEO of Moderna, in the release. “The results presented today are a result of pushing new boundaries in the treatment of cardiovascular and other ischemic vascular diseases and address serious unmet needs with the goal of improving patients’ lives.”

REFERENCE

AZD8601 EPICCURE Phase II trial demonstrated safety and tolerability in patients with heart failure [news release]. AstraZeneca; November 15, 2021. Accessed November 15, 2021. https://www.astrazeneca.com/media-centre/press-releases/2021/azd8601-epiccure-phase-ii-trial-demonstrated-safety-and-tolerability-in-patients-with-heart-failure.html