Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) are a promising tool for assessment of drug-induced arrhythmias during non-clinical drug development. This technology is under evaluation by the FDA’s Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative and the Japanese iPS Cardiac Safety Assessment consortium (JiCSA) to develop new cardiac safety assessment measures to refine current S7B and E14 guidelines.

New cardiac safety testing guidelines are being finalised, as part of the FDA’s Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, which aim to remove the over-reliance on screening against the hERG channel by expanding the panel to include hNav1.5, hCav1.2, hKv4.3/KChiP2.2, hKir2.1 and hKv7.1/KCNE1 human cardiac ion channels.

The Best of Both Worlds: Innovation, Collaboration and Synergy between CROs and their Customer Partners, Stevenage, 2018

Stevens, E.B.; Stephens, G.J. British Journal of Pharmacology. 2018, 175 (12), 2133-2137

Atrial fibrillation (AF) is the most common arrhythmia observed in the clinic, considerable effort has been made to identify the cellular mechanisms of AF and develop new safe and effective antiarrhythmic drugs(1). However, preclinical studies using non-cardiac cells and non-human animal models may not replicate the physiology of human atrial cardiomyocytes or predict patient efficacy and safety.

This talk was presented by Dr Sarah Williams at the Axol Metrion Interactive Stem Cell Forum held in May 2018. This project received funding from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 Research and Innovation Program.

The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is a new cardiac safety testing proposal sponsored by the FDA to refine the current ICH S7B and E14 guidelines. Two components of CiPA utilise in vitro electrophysiological assays that require validation using a toolbox of compounds with defined clinical proarrhythmic risk. Here we outline our progress to optimise these electrophysiological assays to meet the CiPA goal of predicting human cardiac liability.

Presentation by Marc Rogers (Metrion CSO) at the 8th February 2018 SR Live event during Metrion’s 2018 Syndicate Room finance round.

Zidar, N.; Žula, A.; Tomašič, T.; Rogers, M.; Kirby, RW.; Tytgat, J.; Peigneur, S.; Kikelj, D.; Ilaš, J.; Mašič LP. European Journal of Medicinal Chemistry. 2017, 139, 232-241

Presentation from Metrion Biosciences’ external speaker series, Professor Alistair Mathie, Medway School of Pharmacy, 13th October 2017.