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

CSRC—HESI—FDA—SPS CIPA Update Workshop

Following the July 23, 2013 Workshop, HESI, CSRC, FDA and other partners initiated four work streams to move the Comprehensive In Vitro Proarrhythmia Assay (CIPA) forward, including: Regulatory, Ion Channel, In Silico and Myocyte.

This update workshop will bring together global regulators, academicians, drug developers and CRO scientists. The focus of the workshop will be on providing information on the latest project developments with the goal for there to be a high level of participant interaction.

Questions: Contact Jennifer Pierson (jpierson@hesiglobal.org) or Valarie Morrow (valarie.morrow@duke.edu) or visit the CIPA website.

Draft Agenda

8:00am-Introduction Philip Sager, Stanford University/Sager

• Consulting Experts (5min)

8:05am- 10:05am- Overview

• The need for a new approach to assessing the proarrhythmic potential of drugs- Philip Sager, Stanford University/Sager Consulting Experts (15min)
• Mechanisms of ventricular arrhythmogenesis [focused on TdP] Craig T. January, University of Wisconsin School of Medicine and Public Health (15mins)
• Ion Channel selection for in silico modeling – scientific basis for choices Hugo Vargas , Amgen /Derek Leishman, El Lilly (15 mins)
• CIPA overview- key concepts and work streams (to key-up key issues- including # and which channels, proarrhythmia metrics, verification, Phase 1 ECGs (under CIPA), explaining confidence in the science and approach) Gary Gintant, AbbVie (20min)
•  The impact of CIPA on drug development (how it would be implemented) Norman Stockbridge, FDA (15mins)
• Discussion (40mins)

10:05-10:20-Break

10:20am-11:50am- In Silico Modeling

• Overview and scientific approach [Talk to explain to clinicians why they can be comfortable relying on in silico data]?  Natalia Trayanova, Johns Hopkins University (20min)
• Development and validation of the model-Zhihua Li, FDA and Sara Dutta, University of Oxford (20min)
• Proarrhythmia metrics-Gary Mirams, University of Oxford (10min)
• Building a community resource-TBD (10min)
• Discussion (30mins)

11:50am-12:20pm-Working Lunch

12:20pm-1:50pm- Test compound selection and Ion Channel testing approach

• Test compound selection- Process, methodology, and selected compounds for CIPA efforts- David Gutstein, NYU Langone Medical Center (15min)
• Current (pre-CIPA) state of ion channel testing and benefits of standardization Najah Abi-Gerges, University of Liverpool (15min)
• Channel testing metrics and specific testing protocols-Bernard Fermini, Pfizer (15min)
• Discussion (45min)

1:50pm- 3:20pm- Myocyte Efforts and Early Stage Development ECG assessment

• Myocyte overview, key concepts, challenges, and metrics-Leslie Tung, Johns Hopkins University (15min)
•  Myocyte approaches to VSD and MEA testing- core protocols and preliminary data- Jiwen Zhang, GE Healthcare (15min)
•  Role of ECG assessment during clinical development under CIPA and experimental findings - David Strauss, FDA (15min)
• Panel Discussion (45min)
• Academic Perspective- Joe Wu, Stanford University

3:20-3:35pm-Break

3:35pm-5:05pm- What is necessary for CIPA acceptance?

• Panel Discussion

Key additional points to be discussed by the panel

• Viewpoint when there is a CIPA-negative compound with human QT prolongation
• The opportunity to revise current labels of some compounds
• Canada-Colette Strnadova, Health Canada (5min)
• EU- Krishna Prasad, MHRA (5min)
• Japan – Kaori Shinagawa, PMDA (5min)
• FDA- TBD (5min)
• Pharmaceutical developer viewpoint
  • North America/EU-TBD (5min)
  •  Japan – Hiroyuki Fukase, CPC Clinical Trial Hospital  (5min)
• Academic perspective
  • Peter Kowey, Lankenau Heart Group (5min)
  • Joe Wu,  Stanford University (5min)
• Panel Discussion (50min)

5:05- 5:30 Summary and next steps

6:30- 8:30 [Optional] Networking Reception

www.cardiac-safety.org

www.hesiglobal.org

www.fda.gov

www.safetypharmacology.org