Cardiomyocytes for Mechanistic Cardiovascular Safety Liabilities
Date: March 29, 2019
Time: 8:30am to 4:30pm
Location: FDA White Oak Campus
Building 31, Room 1503- Great Room
10903 New Hampshire Avenue
Silver Spring, MD 20993
Registration
Persons interested in attending this public workshop must register online at https://www.eventbrite.com/e/cardiomyocytes-for-mechanistic-cv-safety-liabilities-tickets-54353537895 by 5 p.m. on March 27, 2019.
Background
Cardiovascular safety liabilities remain an important concern in drug development that impacts candidate attrition and may lead to adverse clinical events. These liabilities (as evidenced by various oncology drugs) span the spectrum of arrhythmias, contractile dysfunction, myocardial injury and inflammation, blood pressure control and even valvular dysfunction.
Recently, a variety of quantitative functional, biochemical and imaging biomarkers measured with human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in medium to higher throughput assays have been studied. These assays have the potential of reducing drug-induced cardiotoxicity with novel therapeutics (and promising combination pharmacological therapies) early in drug discovery while reducing reliance on traditional (and often nonspecific) animal toxicity studies. This session will focus on the use of hiPSC-CMs in nonclinical studies to guide early drug discovery efforts in human-relevant models and provide mechanistic insights into cardiac contractile and structural liabilities and recognized failure modes. We will discuss strengths and limitations of current capabilities, describe technical requirements for such a paradigm, cite study examples, and discuss strategies for validating, qualifying and building confidence in the relevance of this approach. Regulatory nonclinical reviewers, experts in the use of hiPSC-CMs, drug developers, and academics will share perspectives on the value of this evolving paradigm, and identify paths forward for appropriate “fit for purpose” applications to be used by industry and regulators to ensure drug safety for patients.
Workshop Information: (documents will be added when available)
- Agenda (PDF)
- List of Speakers and Panelists (PDF)
- Planning Committee:
Xi Yang, FDA (xi.yang@fda.hhs.gov)
Gary Gintant, AbbVie (gary.gintant@abbvie.com)
Jennifer Pierson, HESI (jpierson@hesiglobal.org) - Presentations
- Gintant, Gary, Ph.D. Leveraging Human-Relevant Cardiomyocytes in Nonclinical Studies to Provide Mechanistic Insights into Cardiovascular Safety Liabilities: Overview of Gaps and Challenges
- Anson, Blake, Ph.D. Stemoni: Accelerating the Discovery of New Medicines
- Hansen, Arne. Engineering heart tissues: analysis of contractile force in hiPSC-CM
- Pointon, Amy. Use of cardiomyocyte models for the detection of cardiac contractility
- Abassi, Yama A, Ph. D. Using Electrical Field Stimulation for Maturation of hiPSC Cardiomyocytes, Assessment of Inotropic Compounds and Cardiac Safety Assessment
- Jensen, Brian MD. Myocardial biology of kinase inhibitor cardiotoxicity:Predictable on-target and surprising off-target effects
- Valentin, Jean-Pierre, Ph.D. Secondary pharmacology and off-target profiling as a way to provide mechanistic insights into drug-induced cardiovascular safety liabilities
- Leptak, Christopher, MD, Ph.D. Drug Development Tools (DDTs) Regulatory Perspective
- Lu, Hua Rong, MD Ph.D. Drug-induced Delayed cardiac toxicities in HUMAN Stem Cell-DERIVED CARDIOMYOCYTES
- Mattes, William B., Ph.D. Integrated Response Markers Dealing With the Elephant
- Kanda, Yasunari. Development of in vitro cardiotoxicity assessment for oncology drugs
- Berridge, B.R.,DVM. A Novel Framework for Human-relevant and Failure Mode-based Assessment of Cardiovascular Safety in Nonclinical Drug Development
- Ribeiro, Alexandre, Ph.D. Micropatterned Human iPSC-Derived Cardiomyocytes
- Abi-Gerges,N.Adult Human Primary Cardiomyocytes for Drug-induced Contractility Risk Detection