Cardiotoxicity screening

Cardiotoxicity is a major reason for drug failure and withdrawal

Drug-induced cardiotoxicity remains one of the most common reasons drug development is halted or a drug is withdrawn from the market. During 2011 and 2012, for example, around 28% of potential therapeutics were abandoned during their clinical trials because of safety concerns with cardiovascular issues being the most prevalent cause (1). Post-marketing analysis also shows how cardiotoxicity has resulted in large numbers of drugs being withdrawn from the market following initial approval (2).

With drug development taking years with associated costs reaching into the billions, reducing these rates of attrition is essential. Traditional animals or hERG-overexpression models may slow or miss the cardiotoxic events. When screening a compound for cardiotoxicity, you need a model that is rapid, reliable, and relevant to human physiology.

Cardiomyocytes offer a reliable in vitro human model

This is why we advocate the use of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). These axoCells^TM Cardiomyocytes are true human models and allow for the exploration of all relevant ion channels rather than just the hERG channel. They’re also Comprehensive in vitro Pro-Arrhythmia Assay (CiPA)-validated and can detect APD prolongation and triangulation associated with hERG blockade and Torsades de Pointes (TdP) risk. 

Using iPSC-CMs in this “clinical trials in a dish”  manner allows for incredibly valuable preclinical assessments, which in turn can identify adverse effects sooner, allowing a safer selection of drugs to progress to early-stage clinical trials, and therefore reduce overall rates of attrition.

Our axoCells Cardiomyocytes give those developing drugs the confidence needed when running vital in vitro safety screens. 

 

References

1. Arrowsmith, J. & Miller, P. Phase II and Phase III attrition rates 2011–2012. Nat. Rev. Drug Discov. 12, 569–569 (2013).
2. Onakpoya, I. J., Heneghan, C. J. & Aronson, J. K. Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature. BMC Med. 14, 10 (2016).