FDA Cardiac Safety Workshop

Meeting Description: Cardiovascular safety liabilities remain an important concern in drug development that impacts candidate attrition and may lead to adverse clinical events. These liabilities (as evidenced by various oncology drugs) span the spectrum of arrhythmias, contractile dysfunction, myocardial injury and inflammation, blood pressure control and even valvular dysfunction. Recently, a variety of quantitative functional, biochemical and imaging biomarkers measured with human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in medium to higher throughput assays have been studied. These assays have the potential of reducing drug-induced cardiotoxicity with novel therapeutics (and promising combination pharmacological therapies) early in drug discovery while reducing reliance on traditional (and often nonspecific) animal toxicity studies. This session will focus on the use of hiPSC-CMs in nonclinical studies to guide early drug discovery efforts in human-relevant models and provide mechanistic insights into cardiac contractile and structural liabilities and recognized failure modes. We will discuss strengths and limitations of current capabilities, describe technical requirements for such a paradigm, cite study examples, and discuss strategies for validating, qualifying and building confidence in the relevance of this approach. Regulatory nonclinical reviewers, experts in the use of hiPSC-CMs, drug developers, and academics will share perspectives on the value of this evolving paradigm, and identify paths forward for appropriate “fit for purpose” applications to be used by industry and regulators to ensure drug safety for patients.

Meeting website: https://www.fda.gov/Drugs/NewsEvents/ucm631998.htm