Rechanneling the Current Cardiac Risk Paradigm

 

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Rechanneling the Current Cardiac Risk Paradigm:

Arrhythmia Risk Assessment During Drug Development Without the Thorough QT Study

CSRC/HESI/FDA Workshop to be Held at the FDA White Oak Facility July 23, 2013

 
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 will examine and discuss 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 will convene 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 will seek input from all participating attendees.
 
Key Topics include:
  • 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

o    Preclinical: Tim Hammond

o    Biotechnology and Investment Perspective: Hamish Cameron, SV Life Sciences Advisers, LLP

o    Clinical Development: Peter Kowey, Lankenau Institute for Medical Research

o    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:

o    In Silico Proarrhythmia Assessment: Gary Mirams, University of Oxford

o    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:

o    Pharm Viewpoint: Andrew Erdman, Genentech

o    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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