Moderna, AstraZeneca Tout Encouraging Trial Data for mRNA-Based Therapeutic in Cardiac Health

mRNA-based technology revolutionized COVID-19 vaccine development in the past year or so. Due to their success, companies like BioNTech and Moderna are developing more mRNA-based vaccines against infectious diseases and cancer. 

However, mRNA technology has many more potential applications apart from vaccine development. Companies are using it to deliver instructions to cells to make other types of proteins, such as antibodies, cytokines, and regenerative factors. These can be adapted to treat a myriad of other diseases. 

According to Stéphane Bancel, Chief Executive Officer of Moderna, “mRNA is a compelling therapeutic modality because of its ability to act locally and transiently, while driving dose-dependent protein expression….”

During the American Heart Association’s Scientific Sessions 2021 annual meeting, Moderna presented the results from a Phase 2 clinical trial testing the safety and efficacy of AZD8601, an mRNA-based therapeutic, for heart disease. The study was led by AstraZeneca, and it demonstrates mRNA technologies can go beyond infectious diseases.

For Moderna, it is crucial to expand beyond vaccines for infectious diseases to continue growing and justify their $95 billion valuations. 

Heart failure is very prevalent, with approximately 40 million adults affected globally, and this number is set to increase by almost 50% in the next decade. There is an unmet need that Moderna can address with their therapy.

Stéphane Bancel continued, “The results presented today are a result of pushing new boundaries in the treatment of cardiovascular and other ischemic vascular diseases to address serious unmet needs with the goal of improving patients’ lives.”

mRNA-Based Therapeutic for Cardiac Regeneration

AZD8601 is an mRNA-based therapeutic that is directly injected into patients’ hearts when they undergo coronary artery bypass grafting (CABG). AZD8601 codes for the vascular endothelial growth factor (VEGF-A), which promotes regeneration and growth of blood vessels. 

Compared to other therapeutics, AZD8601 is a “naked” mRNA, which means it is not encapsulated by a lipid layer during delivery. 

In pre-clinical models, AZD8601inproved blood flow after a heart attack. Additionally, in the Phase 1 study, VEGF-A was successfully expressed and well-tolerated following intradermal injection. 

The safety and tolerability of AZD8601 were tested in the AstraZeneca-led Phase 2 clinical trial known as EPICCURE. The randomized, placebo-controlled, double-blind, multicenter study consisted of 11 patients with chronic heart failure, 7 treated with the mRNA therapeutic, and 4 with the placebo. While undergoing CABG, the therapy was injected directly into damaged but viable tissue.  

Results show that AZD8601 was safe and well-tolerated. Additionally, the therapy improved three additional endpoints compared to placebo: 

1. Increased blood flow, as measured by left ventricular ejection fraction
2. Decreased NT-proBNP, a biomarker is elevated in patients with heart failure
3. Improved functional patient-reported outcomes

Although the changes did not reach statistical significance, they provide strong reasoning to test AZD8601 in larger studies. 

“Over one billion heart cells can be lost during a heart attack. 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,” said Mene Pangalos Executive Vice President, BioPharmaceuticals R&D, AstraZeneca.

Author

Daniel Ojeda