Study reports on the first human cellular and metabolomics-based test for the evaluation of drugs for cardiotoxic effects
MADISON, WI –February 20, 2020– Stemina Biomarker Discovery, Inc., today announced study results showing the high performance of the company’s Cardio quickPredict test in identifying cardiotoxic effects for a large number of well-characterized drugs. These results suggest the drug screening test could provide drug developers with an early, highly accurate and more comprehensive evaluation of cardiovascular toxicity. The study, titled “A Targeted Metabolomics-Based Assay Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Identifies Structural and Functional Cardiotoxicity Potential,” was published in the journal Toxicological Sciences on February 10, 2020. The company is offering Cardio quickPredict as a compound safety screening service.
Drug-induced cardiotoxicity is a major challenge throughout the drug discovery and development process and has led to the withdrawal of FDA-approved drugs from the market. Current cell-based preclinical cardiotoxicity testing largely focuses on acute changes in the rhythm of the heart, while testing in animal models are limited due to low-throughput, high-cost, and species-specific cardiac structural and functional differences.
In the study, scientists from Stemina, in consultation with toxicologists from UCB Biopharma SPRL, developed Cardio quickPredict, a biomarker-based platform, to predict cardiotoxicity potential based on changes in the metabolism and viability of human cardiomyocytes (hiPSC-CM) produced by FUJIFILM Cellular Dynamics Inc, Madison, WI, USA.
“We were impressed with the science at Stemina in developing Cardio quickPredict,” said Jean-Pierre Valentin, Senior Director, Head of Investigative Toxicology at UCB Pharmaceuticals. “The test addresses the need for a combined compound safety screening tool to assess risk of both electrophysiological dysfunction and structural damage in a single test and will be useful in compound safety screening.”
In the first part of the study, four biomarker metabolites (arachidonic acid, lactic acid, 2’-deoxycytidine, and thymidine) were identified as indicators of cardiotoxicity in hiPSC-CM following exposure to 66 drugs. These metabolites were used in the second part of the study to develop targeted methods and define predictive thresholds for each of the biomarkers of cardiotoxicity. The combination of these thresholds predicted the cardiotoxicity potential of 81 drugs with 86% balanced accuracy, 83% sensitivity, and 90% specificity.
“This is the first large-scale, metabolomics-based study evaluating both structural and electrophysiological cardiotoxic effects for drugs,” said Jessica Palmer, MS, associate director of toxicology at Stemina and first author on the paper. “With its high degree of accuracy, low cost and high-throughput format, Cardio quickPredict could be used as either a standalone assay or in combination with other tests to help investigators with lead identification or optimization.”
“Regulatory agencies have begun to push for the development of human systems as alternatives to animal testing or as complementary methods for studying the potential health effects of drug-induced cardiovascular toxicity,” said Elizabeth Donley, JD, MBA, MS, chief executive officer of Stemina and an author on the paper. “Implementing better screening tools to identify cardiotoxic effects earlier in the process can significantly reduce cost and time in bringing drugs to patients.”
After a 2013 FDA workshop, the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative was launched with the goal to improve current regulatory guidance by introducing alternative predictive technologies, including human stem cell-derived cardiomyocytes, into preclinical safety assessment. In addition to functional cardiotoxicity, Cardio quickPredict provides an assessment of structural cardiotoxicity, which is a needed endpoint that is not currently represented in the four CiPA Work Streams.
The study was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R44GM100640. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About Stemina Biomarker Discovery
Stemina Biomarker Discovery has developed two key human cellular systems for toxicology and compound safety screening to improve human health and provide an alternative to animal testing. The Company’s Cardio quickPredict uses heart cells differentiated from human stem cells to provide assessment of both structural and functional cardiotoxicity potential of candidate compounds. The company’s companion product, devTOX quickPredict uses human stem cells to screen drug candidates, chemicals, consumer products, tobacco and e-cigarette and cosmetics ingredients for their potential to cause birth defects in the developing human embryo. For more information, please visit our website at http://www.stemina.com.
Elizabeth Donley, CEO
Stemina Biomarker Discovery