NASH Populations with Cirrhosis: Drug Development Challenges and Solutions

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Globally, the incidence of liver cirrhosis caused by NAFLD increased from 178,430 cases in 1990 to 367,780 cases in 2017 — a 106 percent increase — and the incidence is expected to continue growing. Consequently, there is a coming tsunami of patients with cirrhosis secondary to NAFLD and its complications. It is imperative that we find ways to change the natural history for these patients and slow progression of the disease. Treatment for patients with early NAFLD will need to focus on the underlying metabolic disease. However, for patients with cirrhosis, treatment will need to focus on reversing and/or slowing progression of fibrosis. Treatment in patients with portal hypertension may be more challenging as it is not clear at what point fibrosis is no longer reversible in this group, and will require addressing the hemodynamic changes (e.g., shunting) in portal hypertension.

Drug development sponsors face several challenges in conducting clinical trials in patients with cirrhosis secondary to NAFLD. This seminar will review the pathophysiology of cirrhosis and portal hypertension. We will discuss patient populations for drug development, the importance of the placebo response and screen failures, as well as clinical trial designs, drug development pathways and potential biomarkers that may be used in these clinical trials.

Register for this webinar to gain insights on liver cirrhosis from a key opinion leader, John M. Vierling, MD, FACP, FAASLD, AGAF, Professor of Medicine and Surgery, Chief of Hepatology, Director of Baylor Liver Health, Baylor College of Medicine. Dr. Vierling will be joined by Labcorp’s leading NASH scientists, Dr. Claudia Filozof, Dr. Joanne C. Imperial and Dr. Lara Dimick-Santos.

Speakers

Claudia Filozof, MD, PhD, Vice President, Liver Therapeutic Area Head, Global Clinical Development, Labcorp Drug Development

Dr. Claudia Filozof joined Labcorp Drug Development in 2014 and consults on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NAFLD/NASH) research projects, as well as provides medical oversight. She is board-certified in nutrition and metabolism and has broad expertise in diabetes, obesity and related metabolic disorders, including in NAFLD/NASH. Her career spans almost 20 years in academic research, as well as 15 years of experience in the pharmaceutical industry.

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Dr. Filozof led multiple drug development programs in obesity and other metabolic diseases and has been actively involved in NASH clinical development since 2011. She is an active member of the Liver Forum, member of the American Association for the Study of Liver Diseases steatohepatitis working group and the European Association for the Study of Diabetes NAFLD group. She has published multiple manuscripts on obesity, lipids and diabetes as well as four recent review articles in clinical development for NASH.

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Joanne C. Imperial, MD, FAASLD, Senior Medical Director, Cardiovascular, Metabolic, Endocrine, Renal Therapeutic Area, LabCorp Drug Development

Joanne C. Imperial, MD, joined Labcorp as a Senior Medical Director in the Cardiovascular, Metabolic, Endocrine, Renal (CVMER) therapeutic area in September 2020. After obtaining her MD degree from New York Medical College, she pursued fellowships in Nutrition and Metabolism, Gastroenterology and Transplant Hepatology. She spent most of her career in academic medicine and was an Associate Professor at Stanford University Medical Center and Lucille Packard Children’s Hospital where she served as PI in many clinical trials in her specialty area of transplant hepatology, with special interests in autoimmune liver diseases, chronic viral hepatitis and nonalcoholic steatohepatitis/fibrosis.

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Her initial role in pharma was in Medical Affairs at Onyx Pharmaceuticals where she expanded the scope of Nexavar for the treatment of hepatocellular carcinoma in late-phase clinical programs. Subsequently, she moved into Clinical Development and prior to joining Labcorp, spent the last 7 years working on multiple clinical studies in autoimmune disease, NASH, liver fibrosis and advanced cirrhosis.

Joanne was involved in the multidisciplinary Liver Forum since its inception and served as co-chair of the NASH Data Standardization Committee from 2014 to 2016 and co-authored the Forum’s first publication in Gastroenterology in 2017. She is an ongoing member of the Liver Forum cirrhosis working groups and the PSC Forum.

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John M. Vierling, MD, FACP, FAASLD, AGAF, Professor of Medicine and Surgery, Chief of Hepatology, Director of Baylor Liver Health, Baylor College of Medicine

John M. Vierling, MD, FACP, FAASLD, AGAF, is Professor of Medicine and Surgery, Chief of Hepatology and Director of Baylor Liver Health at the Baylor College of Medicine in Houston, Texas. He also serves as Director of Advanced Liver Therapies (a clinical research unit) and Program Director of the Hepatology and Liver Transplantation Fellowship. He obtained his undergraduate degree in Biology with Great Distinction from Stanford University and his MD degree from Stanford University School of Medicine.

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Dr. John M. Vierling’s broad clinical interests and translational research interest in immunologic mechanisms of hepatobiliary injury have facilitated his goal of advancing science to enhance healthcare and education. He has authored over 290 manuscripts and chapters. He is co-editor of Liver Immunology: Principles and Practice, now in its third edition. He is an active member of the International Autoimmune Hepatitis Group. He has served on the Editorial Boards of Hepatology, Liver Transplantation and Gastroenterology.

His honors include: Phi Beta Kappa, Alpha Omega Alpha, Best Doctors in America for the past 21 years, Top 1% physician rating by U.S. News and World Report, Who’s Who in America, in the World, in Science and Engineering, in Healthcare, the Albert Nelson Marquis Lifetime Achievement Award and the 2021 AASLD Distinguished Service Award. He currently serves on the NIH NIDDK Liver Tissue and Cell Distribution System Coordinating Committee and on the DILI Network’s DSMB. He is a former President of the American Association for the Study of Liver Diseases, Secretary-Treasurer of Digestive Disease Week® and Chairman of the National Board of Directors of the American Liver Foundation.

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Lara Dimick-Santos, MD, Executive Medical Director in the Liver Indications Group, LabCorp Drug Development

Dr. Dimick worked at the US Food and Drug Administration (FDA) from 2009 to June 2021. She initially reviewed indications for gastrointestinal diseases and for inborn errors of metabolism (rare diseases). However, eventually she gravitated to review of liver disease indications and has been a major driver in the promotion of drug development for liver diseases since that time. Dr. Dimick was pivotal in the development of surrogate endpoints for clinical trials in nonalcoholic steatohepatitis (NASH) that facilitated the expansion of drug development for NASH. She was the main driver of the development of the clinical outcome endpoint of “progression to cirrhosis” on histopathology, which reduced the length of the clinical trials for many liver diseases by several years, making them feasible. This allowed a large expansion of drug development in liver diseases.

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Dr. Dimick recently joined LabCorp Drug Development as an Executive Medical Director in the Liver Indications Group. Her main role is to provide medical, scientific, regulatory and strategic consultancy advice to LabCorp’s partners in order maximize the value of their asset and facilitate the development of the most efficient drug development programs and clinical trials, primarily for patients with underlying liver diseases but also for other indications. Dr. Dimick remains passionate and committed to promoting drug development for these liver diseases with major unmet medical needs.

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