CSRC, HESI, and FDA to Host CiPA Meeting

The CSRC, Health and Environmental Sciences Institute (HESI), and the FDA will host a two-day meeting titled, “New Advances in the Assessment of Drug-Induced Arrhythmias and the Comprehensive In Vitro Proarrythmia Assay (CiPA),” on May 21-22, 2018 in Washington, D.C.

Discussion topics will include:

  • New approaches to evaluating the propensity of drugs to cause arrhythmias
  • Potential revisions to ICH E14 and ICH S7B Regulatory Guidances
  • Evolving data, ramifications, and potential regulatory implications from the Comprehensive In Vitro Proarrhyhmia Assay (CiPA)
  • The use of statistical methodologies in lieu of a positive control for QT studies
  • Updates from the FDA QT Interdisciplinary Review Team

View the draft agenda and register today!

CSRC Committees Gain New Members

Join us in welcoming Boaz Mendzelevski, MD; Anupam Agarwal, MD, MPH; and Mary Beth Sabol, MD, BSN to CSRC committees. Drs. Mendzelevski and Agarwal joined the Scientific Oversight Committee and Dr. Sabol is now serving as the co-chair of the Membership Committee. Learn more about these members and their expertise by reading their biographies below.

Boaz Mendzelevski, MD: 

Dr. Medzelevski is a consultant cardiologist at Cardiac Safety Consultants Ltd.

He received his degree in medicine from the Ben-Gurion University Medical School and his board certification in internal medicine from the Soroka Medical Center, both located in Beer-Sheva, Israel. He then obtained his board certification in cardiology from the Shaare-Zedek Medical Centre in Jerusalem, Israel. He completed further training in interventional cardiology and electrophysiology at the Royal Brompton Hospital and the National Heart and Lung Institute in London, UK.

Dr. Mendzelevski co-founded the first European pharmaceutical research ECG core laboratory, Cardiac Alert Ltd, in London, UK. It was later acquired by Quintiles, now known as IQVIA. He helped relocate and reinstate the lab in Mumbai, India, where it still operates today. Dr. Mendzelevski later joined Covance and launched its European Cardiac Safety Services group and, after the Covance ECG lab was divested, he joined Medifacts International, later becoming a part of the BioClinica organization, as Vice President of Cardiology.

Currently, Dr. Mendzelevski is focusing on his work as a cardiology consultant to the pharmaceutical and biotechnology industry and provides expert input regarding cardiovascular safety issues in drug development. He is also very active at the Drug Information Association (DIA) and chaired numerous DIA cardiac safety conferences and workshops in the United States, Europe, and Asia (Japan and China). He is a regular speaker and chair at other industry and scientific meetings and has authored numerous peer reviewed publications.

Anupam Agarwal, MD, MPH: 

Dr. Agarwal is a cardiologist with over two decades of experience in treating patients and clinical research in academia in the United States. In the early 90s Dr. Agarwal worked at the Myocardial Infarction Triage and Intervention (MITI) registry with Douglas Weaver at the University of Washington, Seattle. In 2004-2005, he was associate director of Angiography Core Lab at TIMI Study Group at Brigham and Women’s Hospital. Over the span of his career, he was involved with research in genetics of hypertension, drug eluted coronary stents, and drug trials in many therapeutic areas including cardiovascular, respiratory, anti-inflammatory, GI, oncology, and Alzheimer’s disease. Dr. Agarwal has worked in the pharmaceutical industry for more than 11 years (GlaxoSmithKline, Pfizer, Gilead). He is currently the head of the Global Clinical Safety & Pharmacovigilance at Zogenix Inc., a pharmaceutical company developing therapies for rare diseases and central nervous system disorders.

Dr. Agarwal holds a medical degree from the GSVM Medical College, Kanpur, India and a Master of Public Health degree from the Harvard School of Public Health.

Mary Beth Sabol, MD, FACC, BSN: 

Dr. Sabol is a cardiologist with experience in both academic medicine and industry. In the early 2000s, she was a Clinical Assistant Professor of Medicine at the hospital of the University of Pennsylvania and was Assistant Director of the Cardiovascular Nuclear Stress Lab. She subsequently joined Wyeth, then Pfizer, and worked in several different functional areas, including Medical Affairs as the Cardiovascular Therapeutic Area Head, Clinical Research & Development, and then Clinical and Post-Marketing Safety. Her experience includes working in multiple therapeutic areas, including cardiovascular, metabolic, endocrine, infectious diseases and transplantation. Since joining GSK in early 2011, Dr. Sabol has worked in Global Clinical Safety and Pharmacovigilance. She led the development and implementation of eCRFs for cardiovascular events and death to standardize data collection across clinical trials internally within GSK and then subsequently led a similar working group on behalf of CSRC. She is the GSK Clinical Safety representative to PhRMA. Within GSK, she co-chairs the Cardiology Safety Panel and is a member of the QT Safety Panel, the Non-Clinical Cardiovascular Safety Panel, the Central Safety Department Operations Board, and the Safety Advisory Forum.

Dr. Sabol received her BS degree in nursing from the University of Delaware and MD degree from Jefferson Medical College. She completed her residency in internal medicine from the University of Massachusetts Medical Center and fellowships in cardiovascular medicine from Thomas Jefferson University Hospital and in Nuclear Medicine from the Hospital of the University of Pennsylvania.

CSRC Heart Failure Think Tank Planning Committee Opportunities Available

The CSRC is currently recruiting planning committee members to help organize and prepare for the upcoming think tank, “Evaluation of Heart Failure as an Off-target Event in Development of Diabetes and other Non-cardiac Drugs.”

“The evaluation of heart failure, both at baseline and incident cases, in the context of drug development remains challenging. The CSRC will be holding a think tank to explore the current landscape of heart failure ascertainment (baseline, incident, severity, events, and therapy) within the context of drug development in order to inform strategies for evaluation of heart failure during clinical trials both in future trials and in the post marketing arena,” said Dr. Jonathan Seltzer, president of ACI Clinical.

“As advances in therapies for various cardiovascular and non-cardiovascular diseases are being pursued at unprecedented levels, and population age and risk factor burdens increase, the number of patients in clinical trials who are at risk for or who manifest heart failure also continues to rise. New therapeutic approaches, including those targeting non-cardiac diseases such as cancer and diabetes, often affect vasculature, myocytes, renal function, or neurohormonal systems, which may influence the development or progression of heart failure in this population.”

If you are interested in joining the planning committee for this event, please contact us at cardiacsafety@duke.dm.edu.

CSRC Meeting & CSRC Think Tank: Detection, Assessment and Risk Mitigation of Cardiac Safety Signals in Oncology Drug Development

Find slides from our “Detection, Assessment and Risk Mitigation of Cardiac Safety Signals in Oncology Drug Development” think tank below.

October 24, 2017

Day 1

1:15pm-2:30pm Session I: Update on CSRC Activities

Discussion: New ideas and suggestions for 2018

2:30pm-3:00pm Regulatory Science: FDA Paths Forward Mitchell Krucoff, MD (Duke Clinical Research Institute)

3:00pm-5:00pm Session II: Hot Topic- A new FDA Pilot Program for providing pre-market “real time” safety data: Implications for Monitoring CV safety in Oncology Trials in Real Time:

Moderator: Jonathan Seltzer, MD, MBA, MA (ACI Clinical)

  • Presentation of FDA Pilot for digital submission of expedited premarket safety Reports Norman Stockbridge, MD (FDA)
  • Risk: Benefit evaluation of cardiac toxicity in Oncology Drug approvals Bindu Kanapuru, MD (FDA)
  • Best practices for CV safety monitoring. Implications of real-time safety data in oncology clinical trials Susan Dent, MD (Ottawa University)

Discussion: Impact of availability of real time data on CV monitoring. What are the possibilities of pre-market ‘real time’ data for detection/mitigation of CV safety issues? What are limitations (e.g. potential false positives, false negatives)? What process/education changes need to be made to accommodate real time information? Should CSRC actively pursue developing best practices in this area?

  • What are the cardiovascular toxicities germane to oncology drug development? Javid Moslehi, MD (Vanderbilt University)(10mins)
  • What patient CV risk factors should be excluded from what types of oncologic agents Anthony Yu, MD (Memorial Sloan Kettering)(10mins)
  • Redefining Cardiac Eligibility Thresholds in Oncology Trials. Role of the Cardiovascular Core Lab Ana Barac MD, PhD (Georgetown University/Medstar Health)(10 mins)

Discussion: How can cardiologists improve evaluation of potential cardiac signals? Are there assumptions we should avoid that would retard our understanding of toxicities in the oncology population?

Lead Discussant: Anupam Agarwal, MD, MPH (Zogenix)

12:00pm-12:30pm Lunch

12:30pm-2:30pm Session III: Assessment of CV signals

What areas of study design for Phase 2 and Phase 3 oncology studies need to be addressed in order to ensure that CV signals are detected? Are there standard data fields/CRFs that should be completed for suspected CV signals? In what situation will suspected events require adjudication? Do they need to be characterized differently in the oncology population? What is needed for safety reporting?

Moderator: Boaz Mendzelevski, MD (Cardiac Safety Consultants)

  • Oncology Study design for assessment of CV safety endpoints
    • Design considerations for Cardio-oncology studies Boaz Mendzelevski, MD (Cardiac Safety Consultants)(12mins)
  • Utilization of biomarkers for CV safety assessments
    • Serial assessments of serum biomarkers and when they might be considered. Alan Jaffe, MD (Mayo Clinic)(10mins)
    • Cardiovascular imaging endpoints in oncology clinical trials Bonnie Ky, MD (University of Pennsylvania)(10min)
  • Practical considerations for CV safety monitoring
    • Strengths and weaknesses of standardized collection of cardiovascular risk data at baseline and MedDRA coding Anupam Agarwal, MD, MPH (Zogenix)(10mins)

 

October 25, 2017

Day 2

8:00am- 8:10am CSRC Welcome & Goals of the Think Tank- Jonathan Seltzer, MD, MBA, MA (ACI Clinical)

8:10am-9:40am Session I: Translational Medicine and Non-clinical signals of potential cardiac toxicity

What is the current state of non-clinical testing for CV safety? How does evaluation of oncology compounds in Phase 1/1st-in-human oncology studies differ from other compounds? How does mechanism of action and metabolic profile effect evaluation of nonclinical signals?

Moderator: Luana Pesco Koplowitz, MD, PhD (Ducks Flats Pharma)

  • An Overview of Translational Medicine in Cardio-Oncology Luana Pesco Koplowitz, MD, PhD (Ducks Flats Pharma)(10mins)
  • Cardiovascular Oncology: Do We Need Plumbers, Electricians, or Strength Trainers? Gary Gintant, PhD (Abbvie)(10mins)
  • Preclinical Assessment of Potential Small Molecule Kinase Inhibitor-Induced Cardiac Toxicity: Past, Present, and Future Baichun Yang, PhD (FDA)(10mins)
  • Induced Pluripotent stem Cells for Cardiac Safety Assessment and Precision Medicine: Regulatory Research at FDA Ksenia Blinova, PhD (FDA)(10mins)
  • Personalized Assessments of Drug-Induced Cardiac Toxicities Paul Burridge, PhD (Northwestern University)(10mins)
  • Discovery Phase Counterscreening for Functional Cardiotoxicity Mathew Brock, PhD (Genentech)(10mins)

Discussion: How can we characterize cardiac risk more precisely and earlier?

Lead Discussant: Gary Gintant, PhD (Abbvie)

9:40am-10:00am Break

10:00am-12:00pm Session II: Specific CV issues in Oncology Development

For specific areas such as HTN, LV dysfunction, pro-arrhythmia: What are the differences in the oncology population compared to a reference population? Why can’t we extrapolate from non-oncology population? What is the burden on cardiologists in evaluation of potential cardiac safety signals?

Moderator: Richard Steingart, MD (Memorial Sloan Kettering Cancer Center)

Discussion: What is the proper role of a cardiologist in oncology clinical trials? When is cardiac expertise needed at the site? When is cardiac expertise needed in evaluation of signals? Is there a need for a more precise characterization of cardiac events in the oncology population? Should suspected CV events be adjudicated?

Lead Discussant: Javid Moslehi, MD

2:30pm-3:10pm Session IV: Balancing CV risk vs benefit in Oncology Drug Development

Moderator: Jonathan Seltzer, MD, MBA, MA (ACI Clinical)

What are the patient and compound features that should be evaluated in determination of risk vs. benefit? What are the particular issues with respect to CV health/toxicity? How do we weigh these factors? Is there a common framework from which we can work to evaluate the value equation?

Panel Discussion: Regulatory, Industry, Patient, Academia, Payer

Lead Discussant: Jonathan Seltzer, MD, MBA, MA (ACI Clinical)

  • Laleh Amiri-Kordestani, MD (FDA)
  • Richard Steingart, MD (Memorial Sloan Kettering)
  • Jack Singer, MD (CTI Biopharma)

3:10pm- 3:30pm Wrap-up & Next Steps