PELOAcademy|Compatibility of hiPSC-derived cardiomyocytes in cardiac safety assessment of drugsafety
presented by Dr. Jieun An, Nexel Co., Ltd., Republic of Korea
Cardiac toxicity is a major cause of compound attrition during drug development as well as for the withdrawal of drugs already on the market. Although ICH S7B guideline has successfully reduced hERG-related risk issues, concerns remain regarding the accuracy of the assay, as hERG blockade does not always correlate with QT prolongation in patients. With recent advances in stem cell technology, it is now possible to generate human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that recapitulate the native behavior and accurately assess the proarrhythmic potentials of candidate drugs. These cells are being actively studied with high-throughput technology, particularly in connection with the ICH guideline revision (CiPA initiative), for their potential as novel assays for preclinical toxicity testing.
In this context, we aim to introduce NEXEL’s Cardiosight®-S (hiPSC-CMs), aligning with the updated ICH E14/S7B guidelines, and provide practical examples of its applications. Notably, Cardiosight®-S exhibits a purity exceeding 95% of cardiac markers and demonstrates a dose-dependent response to drugs targeting electrophysiological ion channels, suggesting high physiological relevance of the cells. By utilizing Cardiosight®-S, we optimized the evaluation of cardiac safety across four platforms (Axion MEA, Nanion FLEXcyte, CardioExcyte, and Agilent CardioECR) to measure field potential and impedance. In summary, toxicity test using Cardiosight®-S offers a promising alternative for determining cardiac safety risks earlier in drug discovery and preclinical studies to assess compounds’ cardiac liability.
Cardiac toxicity is a major cause of compound attrition during drug development as well as for the withdrawal of drugs already on the market. Although ICH S7B guideline has successfully reduced hERG-related risk issues, concerns remain regarding the accuracy of the assay, as hERG blockade does not always correlate with QT prolongation in patients. With recent advances in stem cell technology, it is now possible to generate human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that recapitulate the native behavior and accurately assess the proarrhythmic potentials of candidate drugs. These cells are being actively studied with high-throughput technology, particularly in connection with the ICH guideline revision (CiPA initiative), for their potential as novel assays for preclinical toxicity testing.
In this context, we aim to introduce NEXEL’s Cardiosight®-S (hiPSC-CMs), aligning with the updated ICH E14/S7B guidelines, and provide practical examples of its applications. Notably, Cardiosight®-S exhibits a purity exceeding 95% of cardiac markers and demonstrates a dose-dependent response to drugs targeting electrophysiological ion channels, suggesting high physiological relevance of the cells. By utilizing Cardiosight®-S, we optimized the evaluation of cardiac safety across four platforms (Axion MEA, Nanion FLEXcyte, CardioExcyte, and Agilent CardioECR) to measure field potential and impedance. In summary, toxicity test using Cardiosight®-S offers a promising alternative for determining cardiac safety risks earlier in drug discovery and preclinical studies to assess compounds’ cardiac liability.