Addressing Drug Candidates’ Cardiotoxicity Risk
The Cardiac Safety SimulatorTM (CSS) is a software solution that integrates physiologically-based pharmacokinetic PBPK modeling and simulation with a cardiomyocyte model to predict the cardiac effects of drugs. It is a standalone product and can be purchased independently of Certara’s Simcyp® Simulator.
Drug-induced cardiovascular adverse events are one of the leading causes of drug withdrawals from the market and of drug label restrictions. As a result, biopharmaceutical companies are keen to identify new drug candidates with a propensity to cause arrhythmias, or the heart to beat with an abnormal rhythm, early in the R&D cycle.
According to the ICH guideline E14, all drugs with systemic exposure must undergo a thorough QT study to investigate QTc prolongation in healthy volunteers at supra-therapeutic doses. However, TQT studies are expensive and some scientists have expressed concern that they may result in the development of some drug candidates being stopped prematurely before the drug’s entire clinical profile has been evaluated.
The U.S. Food and Drug Administration (FDA) and the Cardiac Safety Research Consortium, of which Certara is a member, are currently evaluating alternatives to the TQT study, including biosimulation approaches such as those employed using CSS. Using CSS, researchers can:
- Assess pro-arrhythmic potential by accounting for the inhibition of cardiac ion channels
- Evaluate the impact of demographic, physiological and genetic factors on drug-triggered cardiotoxicity
- Assess the influence of multiple drugs on ventricular ion current and simulated ECGs to account for participants who may be receiving treatment for more than one condition
- Know about potential safety issues sooner: Enhanced QSAR models enable assessment of drug triggered ion channel current inhibition even when in vitro data are not available.
- Maximize investment in software: CSS is connected to the Simcyp Simulator allowing use of the leading platform for population-based IVIVE/PBPK.
- Save time learning complex software: CSS is designed to be intuitive and easy for non-modelers to use.
- All in one tool: A new flexible, Excel-based tool enhances visualization and analysis of simulation results.