AstraZeneca and Medera’s Novoheart develop first human models of heart failure

AstraZeneca (AZ), in collaboration with Novoheart and Medera Biopharmaceuticals, has successfully developed the world’s first human-specific in vitro, functional model of heart failure with preserved ejection fraction (HFpEF).

HFpEF, a steadily worsening condition especially common among the elderly, accounts for approximately 50% of all heart failure cases. Despite this, HFpEF remains poorly understood and previous models of the disease have shown limited ability to mimic its clinical presentation due to the complexities of the condition.

This has meant that drug developers have lacked predictive tools for preclinical testing of drug candidates for HFpEF and clinical outcomes have plateaued over the last several decades.

To tackle this, the partners created the in vitro model using Novoheart’s 3D human ventricular cardiac organoid chamber (hvCOC) tech – mini-Heart – that reproduces key phenotypic characteristics of HFpEF, including relaxation defects, fibrosis and hypertrophy.

Also known as 'human heart-in-a-jar', this model, unlike animal models, uses engineered hvCOCs that can be made with specific cellular and matrix compositions as well as patient-specific human induced pluripotent stem cells that allow control over their physical and mechanical properties to uniquely mimic those observed in HFpEF patient hearts.

Novoheart has also developed human cardiac fibre-like HFpEF cardiac tissue strips that recapitulate the effects of HFpEF on cardiac muscle stiffness and contractility.

Regina Fritsche Danielson, senior vice president, head of research and early development, cardiovascular, renal and metabolism, BioPharmaceuticals R&D, AZ, said, “At AstraZeneca, we recognise the urgent need to learn more about the underlying mechanisms of HFpEF in our ambition to develop targeted therapies for this population of patients.

“Our collaboration with Novoheart to build the first in vitro HFpEF models will help us bridge the gap between animal models and clinical trials to accelerate the drug discovery process by providing human-specific preclinical data.”

Under the terms of the 2019 agreement, Novoheart exclusively owns the intellectual property rights to the newly developed model.

Medera’s chief executive officer, Dr Ronald Li, said: “The US FDA Modernisation Act 2.0 aims to accelerate innovation and get safer, more effective drugs to patients more quickly by encouraging the use of scientifically superior, human-based technologies to replace animal testing for improved human accuracy and therefore better successes.

“Along this line, we are totally excited about the new HFpEF human mini-heart models. We are now focusing on their translation into tangible patient benefits.”