Assessment of BMS-986094-induced chronic cardiotoxicity using human iPS cells-derived cardiomyocytes

【Introduction】 Evaluation of drug-induced cardiotoxicity is important to avoid adverse effects, such as arrhythmia and contractile dysfunction, which is considered to result in heart failure, in non-clinical and clinical studies. For example, BMS-986094, which was developed as a Hepatitis C virus nucleotide polymerase (non-structural 5B) inhibitor, was withdrawn from phase 2 clinical trials because of unexpected heart failure by long-term administration. Although animal models have been widely used to assess cardiac contraction, in vitro models are expected to assess human-specific contraction. We have previously developed the methods to assess cardiac contraction using motion analyses in human iPS cell-derived cardiomyocytes (hiPSC-CMs). Here we assessed whether BMS-986094 induced chronic contractile dysfunction in hiPSC-CMs.