Proarrhythmia liability assessment and (CiPA): An industry survey on current practice.

Abstract

Introduction

The Safety Pharmacology Society (SPS) has conducted a survey of its membership to identify industry practices related to testing considered in the Comprehensive In vitroProarrhythmia Assay (CiPA).

Methods

Survey topics included nonclinical approaches to address proarrhythmia issues, conduct of in silico studies, in vitro ion channel testing methods used, drugs used as positive controls during the conduct of cardiac ion channel studies, types of arrhythmias observed in non-clinical studies and use of the anticipated CiPA ion channel assay.

Results

In silico studies were used to evaluate effects on ventricular action potentials by only 15% of responders. In vitro assays were used mostly to assess QT prolongation (95%), cardiac Ca2 + and Na+ channel blockade (82%) and QT shortening or QRS prolongation (53%). For de-risking of candidate drugs for proarrhythmia, those assays most relevant to CiPA including cell lines stably expressing ion channels used to determine potency of drug block were most frequently used (89%) and human stem cell-derived or induced pluripotent stem cell cardiomyocytes (46%). Those in vivoassays related to general proarrhythmia derisking include ECG recording using implanted telemetry technology (88%), jacketed external telemetry (62%) and anesthetized animal models (53%). While the CiPA initiative was supported by 92% of responders, there may be some disconnect between current practice and future expectations, as explained.

Discussion

Proarrhythmia liability assessment in drug development presently includes study types consistent with CiPA. It is anticipated that CiPA will develop into a workable solution to the concern that proarrhythmia liability testing remains suboptimal.

Read more here: Proarrhythmia liability assessment and the comprehensive in vitro Proarrhythmia Assay (CiPA): An industry survey on current practice. Authier et al. Journal of Pharmacological and Toxicological Methods. Volume 86. July 2017. Pages 34-43.

By |2018-11-22T11:58:28+00:00July 19th, 2018|Ion Channels, Publications|Comments Off on Proarrhythmia liability assessment and (CiPA): An industry survey on current practice.

About the Author:

Dr Michael Morton, PhD, Director and Cofounder, ApconiX, UK, an integrated toxicology and ion channel company that brings together a team of world-renowned nonclinical safety experts with over 400 years of drug discovery and development experience. Mike graduated from the University of Wolverhampton with a degree in Biomedical Sciences and then aspiration to work in hospital pathology. Having finished his Sandwich placement in Clinical Biochemistry at Sandwell Hospital and Mike subsequently gained a MSc in Clinical Biochemistry from the University of Manchester and carried out research into porphyrin metabolism. Moving to the University of Leeds, Mike completed his PhD in Pharmacology at researching adenosine receptor expression in the rat kidney . Mike was introduced to ion channels as a Post-Doc at Leeds and Yale University, patching with the likes of Fred Sigworth and Steve Hebert, then joined the Global Ion Channel Initiative at AstraZeneca. Mike worked at AstraZeneca for eight years before founding ApconiX with Professor Ruth Roberts and Dr Richard Knight. Mike has a serious passion for ion channels. And he’s very good at them . He is a serious scientist (with a serious sense of humour) who wants to make sure that every customer understands the consequences of the results he obtains and works with his colleagues to ensure a better decision is made on drug safety.