Ion men at Metrion star in two US FDA peer review papers
Metrion Biosciences in Cambridge is in five-star global company for a major initiative headlined by the US Food and Drug Administration.
The Granta Park ion channel CRO and drug discovery business joins big hitters from the Cambridge UK life science technology cluster as key contributors to two new peer-reviewed papers under the FDA’s CiPA (Comprehensive in vitro Proarrhythmia Assay) venture.
The papers, in Nature Scientific Reports and Toxicology and Applied Pharmacology, focus on application of improved cardiac safety testing protocols and recommendations for best practice for the drug discovery industry.
CiPA, triggered in July 2013 following a workshop at the FDA, is designed to revise and enhance the regulatory framework assessing cardiac safety of new chemical entities.
Under current guidelines, new therapeutics undergo initial assessment of proarrhythmic risk by measuring activity against the hERG cardiac ion channel, before progressing to studies in preclinical animal models and ultimately, a Thorough QT interval study in the clinic.
CiPA aims to extend the use of advances in early electrophysiology-based cardiac ion channel screening, in silico predictive modelling, and human induced pluripotent stem cell derived cardiomyocytes to improve the accuracy and reduce the cost of predicting the cardiac liability of new drug candidates.
Metrion’s research forms part of the first stage of the proposed harmonisation work, to provide clarity on how to standardise cardiac ion channel assays to ensure they deliver consistent data for in silico models of clinical cardiac arrythmia risk.
The first paper, published in Nature Scientific Reports by an international group of authors drawn from 20 different commercial and academic laboratories, including Metrion Biosciences, was coordinated by the Health and Environmental Sciences Institute (HESI).
It reviews data from a multi-year, multi-site collaboration across industry, academia and the FDA regulatory agency to optimise experimental protocols and reduce experimental variability and bias.
The goal of the study was to guide the development of best practices for the use of automated patch clamp technologies in early cardiac safety screening.
High quality in vitro cardiac ion channel data is required for accurate and reliable characterisation of the risk of delayed repolarisation and proarrhythmia in the human heart and to guide subsequent clinical studies and regulatory submissions.
The second paper, to be published formally in Toxicology and Applied Pharmacology paper on May 1 but currently available online, uses automated patch clamp data from the CiPA consortium to address the lack of statistical quantification of variability, which hinders the use of primary hERG potency data to predict cardiac arrhythmia. The consortium establishes a more systematic approach to estimate hERG block potency and safety margins.
Dr Marc Rogers, CSO at Metrion Biosciences, said: “The Metrion team has been a participant in the international CiPA Initiative since inception and we are now pleased to be able to announce the publication of our data from this global collaborative scientific effort.
“We believe these projects will make a significant contribution to the eventual revision of cardiac safety testing guidelines by the FDA and other international regulatory agencies.
“They also contribute to deepening our knowledge of the underlying causes of proarrhythmia, which will help prevent early attrition of potentially promising drugs.”
Cambridge-linked companies that have contributed to one or both of the review papers include AstraZeneca, Charles River Laboratories, GlaxoSmithKline, Pfizer; Sanofi R & D; Bristol-Myers Squibb and Bayer AG.
Metrion Biosciences was formed in September 2015 following a management buyout of Xention Limited’s contract research business. It provides drug discovery services for ion channel targets to clients on a fee-for-service or collaboration basis and is also a leading provider of cardiac safety profiling, cardiac translational assays and neuronal translational assays.