Heart-in-a-Jar Collaboration Could Accelerate Drug Discovery for Heart Failure

Heart failure is a chronic disease that impacts millions of people around the globe and has an estimated economic burden of about $100 billion annually. Despite those high numbers of cases, drug developers have not had the most effective models for the preclinical testing of drug candidates. That could change.

This morning, AstraZeneca and Canada-based NovoHeart announced a collaboration to develop a first-of-its-kind, functional miniature human heart model of heart failure. The announcement boosted NovoHeart’s stock more than 23%.

The so-called “heart-in-a-jar” will be created from human stem cells and designed to reproduce key phenotypic characteristics of heart failure. That failure will include preserved ejection fraction, a common condition especially among the elderly and in women. Heart failure with preserved ejection fraction (HFpEF) is a common condition especially among the elderly and in women. There is a reported prevalence approaching 10% in women over the age of 80 years. The collaboration with AstraZeneca’s Cardiovascular, Renal and Metabolism therapy area aims to provide a very unique solution for future assessment of novel therapeutics. For AstraZeneca, the collaboration comes weeks after the U.S. Food and Drug Administration approved its SLG2 inhibitor Farxiga to reduce the risk of hospitalization for heart failure in type 2 diabetes patients who have these types of cardiovascular concerns.

HFpEF accounts for approximately 50% of heart failure cases, the companies noted this morning. Despite those numbers, NovoHeart and AstraZeneca said its pathological mechanisms and diverse etiology are poorly understood. Current disease models have limited ability to mimic the clinical presentation of HFpEF, NovoHeart said. As a result, clinical outcomes for HFpEF have not seen much improvement over the years.

The heart-in-a-jar is a new in vitro model that used NovoHeart’s proprietary 3-D human ventricular cardiac organoid chamber (hvCOC) technology. That platform reproduces key phenotypic characteristics of HFpEF. According to the announcement, the hvCOC is the only human-engineered heart tissue available on the market to date that enables clinically informative assessment of human cardiac pump performance including ejection fraction and developed pressure. The in vitro model is different than animal models because engineered hvCOCs can be fabricated with specific cellular and matrix compositions, and patient-specific human induced pluripotent stem cells (iPSCs), that allow control over their physical and mechanical properties to mimic those observed in HFpEF patient hearts, the company said this morning. The in vitro platform will provide a unique assay for understanding the mechanisms of HFpEF, identification of new therapeutic targets, and assessment of novel therapeutics for treating HFpEF patients.

Regina Fritsche Danielson, head of Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, at AstraZeneca, said there are “significant unmet treatment needs” in patients with heart failure with preserved ejection fraction. Combining the NovoHeart hvCOC model with AstraZeneca’s expertise in heart failure, Danielson said the hope is to accelerate the drug discovery process by providing human-specific preclinical data.