Rechanneling the Current Cardiac Risk Paradigm: Arrhythmia Risk Assessment During Drug Development Without the Thorough QT Study

  • Start Date/Time :
  • Location : Silver Spring, Maryland, USA
Drug-induced proarrhythmia is a major safety issue in pharmaceutical development that markedly impacts drug discovery and development. The current approach identifies many drugs as being “positive’ despite having no demonstrable proarrhythmic risk. This results in adverse labeling for some compounds and can inhibit the development of new clinical entities due to concern of possible QT signals and the subsequent complexities of the clinical development pathway.
This workshop examined and discussed a new paradigm, focusing on a comprehensive assessment of ion channel effects to determine actual proarrhythmic risk. This new approach has the real potential to obviate the need for clinical Thorough QT Studies, making
CV risk assessment more efficient.
Experts and opinion leaders from academia, industry and regulatory agencies in the US, EU, Canada, and Asia convened to discuss what a new framework might look like, the benefits and limitations of the current guidelines, and the need for a uniform assay schema. The workshop sought input from all participating attendees.
Key Topics included:
  • Paradigm Shift: New Approach to Assessing Torsade de Pointes Risk without the Thorough QT Study
  • Benefits and limitations of the current paradigm as outlined in ICH S7B and E14
  • Proposed Proarrhythmia Assay Schema
  • Validation concepts pertaining to the new approach and the tension surrounding risk
  • What success would look like and how the approach would be used
  • Post-marketing determination of arrhythmia risk
  • Regulatory acceptance, Pharmaceutical Perspective, and Labeling Implications

CSRC-HESI-FDA Meeting Agenda

Rechanneling the Current Cardiac Risk Paradigm:  Arrhythmia Risk Assessment During Drug Development Without the Thorough QT Study

10903 New Hampshire Avenue, Silver Spring, Maryland 20993
White Oak Facility, FDA Headquarters • Silver Spring, MD • July 23, 2013

8:10 a.m. – 9:30 a.m.    Session 1: Paradigm Shift: New Approach to Assessing TdP Risk without the Thorough QT Study Moderators: Stockbridge/ Sager

Benefits and limitations of the current paradigm as outlined in ICH S7B and E14

  • Overview: Norman Stockbridge, FDA 
  • Impact of the current paradigm on drug discovery and development
    • Preclinical: Tim Hammond 
    •  Biotechnology and Investment Perspective: Hamish Cameron, SV Life Sciences Advisers, LLP 
    • Clinical Development: Peter Kowey, Lankenau Institute for Medical Research 
    • Regulatory Risk, Uncertainty and Implications: Krishna Prasad, EMA
  • Beyond S7B/E14 - Why the science supports a new paradigm: John Koerner, FDA
  • FDA Policy Viewpoint: Robert Temple, FDA  
  • Audience/Panel (All Speakers) Discussion Lead discussant: Christine Garnett, Certara

10:45 a.m. - 11:00 a.m. Break

11:00 a.m. - 12:30 p.m. Session 2: Proposed Assay Schema Moderators: Koerner, Valentin,& Gintant

  • Mechanisms of arrhythmogenesis: Craig January, University of Wisconsin
  • Overview and why certain assays were included and others not: Gary Gintant, AbbVie
  • Individual approaches contributing to the Schema:
    • In Silico Proarrhythmia Assessment: Gary Mirams, University of Oxford
    • Stem cell Proarrhythmia Assessment: Joseph Wu, Stanford University
  • Audience/Panel (all speakers and Dr. Stockbridge) Discussion Lead discussant: Dan Roden, Vanderbilt University

12:30 p.m. - 1:00 p.m.   Working Lunch

1:00 p.m. - 3:00 p.m.     Session 2: Proposed Assay Schema Continued

  • Validation concepts pertaining to the new approach and the tension surrounding risk: Brian Berridge, GSK
  • What success would look like, how the approach would be used, and next steps with respect to Schema refinement: Jean-Pierre Valentin, AstraZeneca
  • Audience/Panel (All speakers and Drs. Roden and Stockbridge) Discussion Lead discussant: Peter Hoffmann, Novartis

3:00 p.m. - 3:15 p.m.     Break

3:15 p.m. - 5:20 p.m.     Session 3: Implications and Next Steps Moderators: Prasad/ Hammond

  • Regulatory acceptance: Krishna Prasad
  • Regulatory Acceptance: Pharm Perspective: Jim Keirns, Astellas
  • Labeling Implications:
    • Pharm Viewpoint: Andrew Erdman, Genentech
    • FDA Viewpoint: Doug Throckmorton, FDA
  • Audience/Panel Discussion (all speakers and Dr. Sager) /Case Scenarios Lead discussant: Charles Benson, Eli Lilly & Co.

5:20 p.m. - 5:50 p.m.     Summary and Next Steps Moderators: Stockbridge, Sager, & Gintant

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