Heart failure

AHA: AstraZeneca and Moderna highlight the potential of mRNA in heart failure


Although AstraZeneca and Moderna are rivals in the COVID-19 vaccine space, the two have an interesting mRNA pact that has worked largely under the radar.

For years, the couple have quietly used Moderna’s mRNA technology to help patients with heart disease (as well as other illnesses), and new interim data released today offers a silver lining that, apart from infectious diseases, this platform could have a wider reach.

We know that mRNA players such as BioNTech, Moderna and CureVac all research influenza and cancer with their technology, having already quickly proven effective in treating SARS-CoV-02, but heart failure can also be a viable target.

As of around 2017, AstraZeneca and the then little-known pre-IPO and pre-COVID Moderna had been working on several mRNA assets for heart disease.

One of these therapies, AZD8601, encodes vascular endothelial growth factor (VEGF-A), a protein that induces the growth of blood vessels, and has now, in a phase 2a test, achieved its primary endpoint of achieving safety and tolerability in patients with cardiac disorders. failure.

RELATED: AstraZeneca and Moderna award contract for mRNA heart failure drug

The data, officially released at the American Heart Association Scientific Sessions on Monday, was the first from a clinical trial injecting what AZ calls “naked” mRNA directly into the hearts of patients undergoing coronary artery bypass grafting (PAC ) elective.

It works as an mRNA-based therapy, with mRNA formulated in citrate saline buffer in the absence of lipid encapsulation that encodes VEGF-A for topical administration in patients undergoing coronary artery bypass grafting. The idea is that it can help the heart spur to heal after damage.

We don’t know if this can work on a large scale because, so far, we are getting a peak in a small study consisting of only 11 patients of which seven were treated with AZD8601 and four received placebo injections.

But AZ and its partner Moderna said that “trends were observed in all three exploratory endpoints of efficacy,” namely: left ventricular ejection fraction, NT-proBNP – a biomarker that measures level of a hormone and is elevated in patients with heart failure – and the functional patient results reported compared to placebo.

“Although the data is limited to show a significant effect, it gives AstraZeneca the opportunity to move on to further trials with AZD8601,” said UK Big Pharma. There are still many unanswered questions and more in-depth testing to be done, but the pair are at least confident enough to take the next step.

“Over a billion heart cells can be lost in a heart attack,” said Mene Pangalos, executive vice president of biopharmaceutical R&D at AstraZeneca.

“These early results indicate the potential of mRNA-based therapies to stimulate the production of VEGF-A to provide restorative and disease-modifying options for patients with heart failure and other ischemic vascular diseases.”

Entresto by Novartis is one of the newer drugs to be approved for heart failure, although the disease, and heart disease in general, remains a major unmet medical need worldwide.