The Cardiac Safety Committee convened a 2-day workshop to discuss mechanistic approaches to cardiovascular safety assessment.
Cardiac Safety Committee 2018 Workshop
May 15, 2018 – May 16, 2018
Boston, Massachusetts, 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.
The HESI Cardiac Safety Committee seeks Postdoctoral or Early Career researchers working in cardiovascular safety science or related field for the Early Career Seminar Award Series. This award offers an opportunity to share your research, learn from and network with experts in the toxicology and safety pharmacology fields from academia, regulatory agencies and pharmaceutical companies.
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:
Ksenia Blinova, PhD (US Food and Drug Administration)
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.
A 3-phased project was conducted by the HESI Pro-Arrhythmia Working Group starting with a detailed literature review and followed by a collaborative HESI-FDA database of 150 new drug candidates to evaluate how predictive nonclinical studies are to clinical outcomes.
Leadership Team:
Jose Vicente Ruize, 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)
Sandy Eldridge, PhD (National Cancer Institute)
HESI Staff:
Jennifer Pierson, MPH
Claire O’Brien, 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)
The Cardiac Safety Steering Team established this subteam in early 2020 to develop and provide a structured resource for use when identifying compounds appropriate in a planned committee study. The database was published April 2024.
HESI Staff:
Jennifer Pierson, MPH
HESI has been awarded a multi-year U01 grant from the US FDA on the “Evaluation of Integrated Human-Relevant Approaches to Identify Drug Induced Cardiovascular Liabilities.” This grant supports HESI in funding and managing novel, in vitro experimental studies to develop targeted mechanistic data to inform drug safety assessment for key cardiac “failure modes.”
HESI received a Broad Agency Announcement (BAA) award from the US FDA to manage a multi-site study on manual and automated patch clamp platforms. The original study included 4 ionic currents (hERG, Nav1.5 peak, Nav1.5 late and Cav1.2) and 14 compounds and has been expanded to include a total of 28 compounds. The project aims to collect additional information on inter-laboratory variability as well as support the FDA in silico model. Learn more about the recommended ion channel protocols and in silico model here.
UCB
US Food and Drug Administration
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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.
Toxicologic Pathology, 2013
Cardiac troponin (cTn) has been utilized to assess acute myocardial injury, but the cTn response in active/ongoing chronic injury is not well documented.
Regulatory Toxicology and Pharmacology, 2013
Cardiovascular (CV) safety concerns are a significant source of drug development attrition in the pharmaceutical industry today.
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.
International Journal of Toxicology, 2011
There are several recent examples where clinically significant, safety-related, drug effects on hemodynamics or cardiac function were not apparent until large clinical trials were completed or the drugs entered the consumer market.
Toxicologic Pathology, 2010
We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury.
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).
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