FDA Workshop on Leveraging Human-Relevant Cardiomyocytes in Nonclinical Studies to Provide Mechanistic Insights into Cardiovascular Safety Liabilities
FDA Cardiac Safety Workshop
March 29, 2019
Silver Spring, Maryland, USA
The mission of the HESI Cardiac Safety Committee is to improve public health by reducing unanticipated cardiovascular-related adverse effects from drugs or chemicals, and to develop innovative approaches to support early detection and prediction as well as improved understanding of cardiovascular toxicology and pathobiology.
This group is working to understand and characterize use of stem cell–derived cardiomyocytes in cardiac safety assessments. An article that included best practices for use of stem cell cardiomyocytes in cardiac safety assessments was published in Regulatory Toxicology and Pharmacology. A new group is planning a study to explore in vitro assay ability to detect cardiotoxicity.
Leadership Team:
Gary Gintant, PhD (AbbVie)
Godfrey Smith, PhD (University of Glasgow)
HESI Staff:
Jennifer Pierson, MPH
This working group is dedicated to investigating mechanisms of proarrhythmic risk. They continue to collaborate with the CiPA Initiative and ICH, and recently published its anticipated high throughput systems (HTS) ion channel work. A new subteam is scoping a conduction/ sodium channel paper to discuss the history and challenges surrounding this topic.
Leadership Team:
John Koerner, PhD (US Food and Drug Administration)
Jean-Pierre Valentin, PhD (UCB Biopharma)
HESI Staff:
Jennifer Pierson, MPH
This working group has examined the sensitivity within a preclinical species to assess the function of contractility. They continue their partnership with University of Surrey and Imperial College London on a mathematical model to predict blood pressure changes. The Implanted Telemetry Subteam explored the impact of telemetry lead placement in toxicology studies (a collaboration with the Pro-Arrhythmia Working Group).
Leadership Team:
Michael Pugsley, PhD (Cytokinetics)
Brian Berridge, DVM, PhD (National Institute of Environmental Health Sciences, National Toxicology Program)
HESI Staff:
E’Lissa Flores, PhD
This working group is dedicated to investigating preclinical cardiac biomarkers of hypercoagulability induced under a thrombotic state, in both normal and diseased states. A manuscript was submitted detailing a study investigating the effects of doxorubicin in Zucker diabetic fatty rats. A new study is in the planning stages using xenobiotics to induce the procoagulant state and confirm measurements of biomarkers of interest.
Leadership Team:
Eric Schultze, PhD (Eli Lilly & Company)
Marjory Brooks, DVM (Cornell University)
HESI Staff:
E’Lissa Flores, PhD
The Cardiac Safety Steering Team established this new subteam in early 2020 to develop and provide a structured resource for use when identifying compounds appropriate in a planned committee study. Delivery of this publicly accessible database is anticipated by the end of 2020.
HESI Staff:
Jennifer Pierson, MPH
This subteam was organized in May 2020 in response to the ongoing pandemic. Subteam members identified that emerging treatments for the novel coronavirus may have cardiotoxicities. The group is exploring how to gather cardiac safety data on five emerging therapies, whether prospective or retrospective, and develop a publication.
HESI Staff:
Jennifer Pierson, MPH
National Institute of Environmental Health Sciences, National Toxicology Program
US Food and Drug Administration
March 29, 2019
Silver Spring, Maryland, USA
FDA Workshop on Leveraging Human-Relevant Cardiomyocytes in Nonclinical Studies to Provide Mechanistic Insights into Cardiovascular Safety Liabilities
May 15, 2018 – May 16, 2018
Boston, Massachusetts, USA
The Cardiac Safety Committee convened a 2-day workshop to discuss mechanistic approaches to cardiovascular safety assessment.
June 18, 2015 – June 19, 2015
Alexandria, Virginia, USA
This meeting was held 18-19 June 2015.
December 11, 2014
Silver Spring, Maryland, USA
This update workshop brought together global regulators, academicians, drug developers, and CRO scientists. The focus of the workshop was on providing information on the latest project developments with the goal for there to be a high level of participant interaction.
October 13, 2013 – October 17, 2013
Research Triangle Park, North Carolina, USA
This workshop was co-sponsored by the HESI Cardiac Safety Committee.
September 2, 2013 – September 4, 2013
Interlaken, Switzerland
HESI gave several presentations at Eurotox 2013.
Journal of Pharmacological and Toxicological Methods, 2010
Cardiovascular safety concerns are a significant cause of attrition in the development of new drugs (Lasser et al., 2002).
Journal of Pharmacological and Toxicological Methods, 2009
Drug-induced ventricular arrhythmia and Torsades de Pointes remain a serious public health issues in bringing safe new pharmaceuticals to the market place.
International Journal of Toxicology, 2018
Results from this limited retrospective electrocardiogram analysis suggest that JTpca and Tpeca may discriminate selective IKr blockers and multichannel blockers and could be considered in the context of an integrated comprehensive proarrhythmic risk assessment.
Journal of Pharmacological and Toxicological Methods, 2013
The evaluation of cardiovascular side-effects is a critical element in the development of all new drugs and chemicals.
Journal of Pharmacological and Toxicological Methods, 2017
The importance of drug-induced effects on the inotropic state of the heart is well known. Unlike hemodynamic and cardiac electrophysiological methods, which have been routinely used in drug safety testing for years, the non-clinical assessment of drug effects on myocardial contractility is used less frequently with ...
Clinical Chemistry, 2008
Information is needed regarding analytical characteristics of cardiac troponin (cTn) assays used in preclinical studies.
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