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 is excited to announce the winners for the committee’s new Early Career Seminar Award Series. This award offers an opportunity for postdocs and early career scientists to share their research, learn from, and network with experts in the toxicology and safety pharmacology fields from academia, regulatory agencies, and pharmaceutical companies. Awardees receive a $500 USD award and are invited to present their research on a public webinar with Cardiac Safety Committee members and other invited guests.
Three awardees were selected for this inaugural Seminar Series:
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:
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 2022.
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
Associate Director for Program Development & Resourcing
jpierson@hesiglobal.orgNational Institute of Environmental Health Sciences, National Toxicology Program
US Food and Drug Administration
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.
Frontiers in Pharmacology, 2019
Contractility of the myocardium engines the pumping function of the heart and is enabled by the collective contractile activity of its muscle cells: cardiomyocytes. The effects of drugs on the contractility of human cardiomyocytes in vitro can provide mechanistic insight that can support the prediction of clinical cardiac drug ...
Frontiers in Pharmacology, 2019
Drug-induced effects on cardiac contractility can be assessed through the measurement of the maximal rate of pressure increase in the left ventricle (LVdP/dtmax) in conscious animals, and such studies are often conducted at the late stage of preclinical drug development. Detection of such effects earlier in drug research using ...
Toxicological Sciences, 2019
A consortium, multi-site approach to testing in vitro assay technology for prediction of drug-induced TdP. The authors sought to test calcium transient assays using the CiPA 28 drugs.
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.
Cell Reports, 2018
The HESI Cardiac Safety Myocyte Subteam completed a validation study with the CiPA 28, two commercial human cardiomyocyte cell lines, 5 devices across 10 sites. The results are published here.
Toxicological Sciences, 2018
hesi@hesiglobal.org
Phone: +1-202-659-8404
Fax: +1-202-659-3859
740 15th Street NW, Suite 600
Washington, DC 20005
Sign up for our monthly e-newsletter.