NASH: Who are the Patients with a Progressive Disease?
Nonalcoholic fatty liver disease (NAFLD) is the most common etiology of chronic liver disease and cirrhosis in developed countries. In spite of the progress in the understanding of pathophysiology there are still many uncertainties in the diagnostic approaches and evaluation, and there is no approved therapy for NASH. The frequency and clinical correlates of NAFLD phenotypes, the progression from fatty liver (FL) to steatohepatitis (or regression from NASH to FL) and the progression or improvement in hepatic fibrosis remain uncertain. In addition to specific genetic predispositions associated with more severe disease in subsets of patients (e.g. PNPLA3 I148M mutation) both disease activity and disease stage affect progression to cirrhosis. In this webinar, Dr. Arun Sanyal will discuss risk factors for disease progression and the implications in clinical development and the need of pharmacological intervention.
Detection and Assessment of Drug Induced Liver Injury (DILI) in NASH Clinical Trials
Drug induced liver injury (DILI) is a leading cause of acute liver failure and transplantation in western countries; and although rare, represents a serious clinical problem due to its unpredictable nature and possibly fatal course. There is no clear evidence of increased risk of DILI in NASH patients, however patients with advanced NASH may have worse outcome when DILI occurs. Patients with NASH have, in general, mild to moderate elevations in liver aminotransferases. However, Hy’s law may be difficult to apply to all NASH patients, especially those with baseline ALT>3x ULN. Dr. Arie Regev will address specific questions related to the detection, assessment and monitoring of DILI in NASH patients.
Adaptive Trial Design in a NASH Development Program
The increasing prevalence, the associated health burden and the lack of approved therapy for patients with NASH represents a substantial unmet medical need. Unfortunately, the long and asymptomatic natural history of the disease, the uncertainties about the disease progression, the fact that most patients are undiagnosed, and the requirement for sequential liver biopsies, creates substantial challenges for clinical development. Adaptive trial designs are being increasingly looked at as a way to streamline the development path and optimize the time to development without compromising on the quality of the evidence needed to establish the efficacy and safety of therapeutic agents. Dr. Claudia Filozof will discuss the strategic framework of applying a seamless adaptive design in a NASH development program. Tammy McIver will describe the statistical considerations.
Arun, Sanyal, MD, Professor of Medicine and Chairman of Gastroenterology Division, Virginia Commonwealth University School of Medicine
Dr. Sanyal is a professor of Medicine and chairman of the Gastroenterology Division at Virginia Commonwealth University (VCU) Medical Center in Richmond, Virginia. Dr. Sanyal also serves as chairman of the NIH NASH Clinical Research Network. His research interests include NAFLD, NASH, animal models of NASH, TIPS, fibrosis, Hepatitis C treatments, NASH clinical trials, as well as clinical studies in liver disease, hepatic neovascularization and genesis of TIPS stenosis and the development of effective therapy of non-alcoholic steatohepatitis.
He is a member of the Scientific Advisory Board at Galmed Pharmaceuticals Ltd. and as a member of the Clinical Advisory Board. Additionally he is a member of the Scientific Advisory Board for Hepatic Clinical Medicine for Cardax Pharmaceuticals, Inc. and a Member of Scientific Advisory Board at Exalenz Bioscience Ltd. Dr. Sanyal is a member of the American Association for Study of Liver Diseases and the American College of Gastroenterology. He is also the president of the American Association for Study of Liver Diseases.
Dr. Sanyal earned his medical degree and completed a residency in Internal Medicine from the All India Institute of Medical Sciences in New Delhi. He also completed a residency in Internal Medicine at Texas Tech University Health Sciences Center in Amarillo, Texas, and a fellowship in Gastroenterology and Hepatology at VCU Medical Center, until being named professor of Internal Medicine, Gastroenterology, Hepatology and Nutrition.
Dr. Sanyal is the author of more than 100 articles in publications including, Gastroenterology, Hepatology and Journal of Infectious Diseases.
Claudia, Filozof, MD, PhD, Executive Medical Director in CVM/ER Therapeutic Area, Covance
Claudia Filozof is Executive Medical Director at Covance/LabCorp. She is currently responsible and consultant for NAFLD/NASH projects.
Dr. Filozof is board certified in Nutrition and Metabolism and has broad expertise in diabetes, obesity and related metabolic disorders, including in non-alcoholic fatty liver disease and steatohepatitis (NAFLD/NASH). Her career spans almost 20 years in academia and more than 12 years of service in the Pharmaceutical industry.
Dr. Filozof served as director of the postgraduate course of obesity and complications in the John F. Kennedy University in Buenos Aires, Argentina. She was editor-in-chief of the Argentine Society of Obesity Journal and member of the initial editorial board of the international journal Obesity Reviews. She also participated as a member of the first WHO task force in obesity management.
Dr. Filozof has been actively involved with the NASH community for the last 5 years. She is a member of the Liver Forum and the data standardization working group. She is also a member of the AASLD steatohepatitis working group and EASD NAFLD group. She has published multiple manuscripts in obesity, lipids and diabetes, including a recent review article “Non-Alcoholic Steatohepatitis: Limited Available Treatment Options but Promising Drugs in Development and Recent Progress Towards a Regulatory Approval Pathway”.
Arie, Regev, MD, Head of the Safety Advisory Hub, Eli Lilly and Company
Dr. Regev received his BSc and MD degrees from the Hebrew University in Jerusalem, Israel. He completed his residency in Medicine and fellowship in Gastroenterology at Rabin Medical Center and Tel Aviv University, where he continued working as attending physician and Associate Chief of Medicine. He subsequently completed clinical fellowship in Hepatology and Transplant Hepatology at the Division of Hepatology of the University of Miami, and Jackson Memorial Hospital in Miami, Florida.
After his fellowship he continued working in the Division of Hepatology as full-time faculty and subsequently Associate Professor of Medicine and Director of the Hepatology Fellowship Program until 2007. Dr. Regev has conducted numerous clinical trials in the field of viral hepatitis and liver transplantation. He was the principal investigator of a number of NIH funded clinical trials and has served as principal investigator on several investigator initiated and industry supported clinical trials in the area of viral hepatitis and liver transplantation.
He is the author of numerous publications in major medical Journals including American Journal of Gastroenterology, Clinical Gastroenterology and Hepatology, Journal of Hepatology, Liver Transplantation, Gut, Transplantation, Proceedings in Transplantation, and Digestive Diseases and Sciences. He authored several chapters in major medical textbooks including Schiff’s Diseases of the Liver, The Clinician’s Guide to Liver Disease, Viral Hepatitis, Requisites in Gastroenterology and Advances in Internal Medicine.
Dr. Regev received Teaching and Research Awards at the University of Miami as well as Tel Aviv University. He served as an active member of the Training and Clinical Policy Committee of the American Association for the Study of Liver Diseases. In January 2007 Dr. Regev joined Eli-Lilly in a Hepatology Consulting position and as Chair of the Liver and GI Safety Committee in the Global Patients Safety organization. He is currently an adjunct associate professor of medicine at the Division of Gastroenterology and Hepatology of Indiana University, and he heads the Safety Advisory Hub at Eli Lilly and Company.
Tammy, McIver, MSc, CStat, Senior Manager, Biostatistics and Statistical Programming, Covance
Tammy has 20 years’ experience in clinical drug development. During this time she has led a team of statisticians and had full responsibility and accountability for all statistical activities on a global product level resulting in registration and market access.
Prior to joining Covance in 2015, Tammy spent 15 years in the Pharmaceutical industry and 4 years at the Medical Research Council. She has broad statistical experience in a range of therapeutic areas including analgesia, cardiovascular, respiratory and oncology. Tammy has supported clinical studies and clinical development programs with adaptive design components.
A chartered statistician with a master’s degree in applied statistics, she is currently lead statistician for a Phase III/IV adaptive design study in NASH and provides statistical consultancy on NASH clinical development programs.
Who Should Attend?
Senior level professionals involved in clinical operations & clinical development, plus medical directors.
Covance is one of the world’s largest and most comprehensive drug development services companies, with annual revenues greater than $2 billion and more than 12,000 employees in more than 60 countries.