Conference | Virtual

Event Title

Use of Biomarkers for Diagnosing and Assessing Treatment Response in Noncirrhotic NASH Trials

September 18 - 19, 2023

Date:: September 18 - 19, 2023
Day1:: Mon, Sep 18 9:00 AM - 4:45 PM ET
Day2:: Tue, Sep 19 9:00 AM - 5:15 PM ET

Topics & Presentations Day 1	Speakers
Use of Biomarkers for Diagnosing and Assessing Treatment Response in Noncirrhotic NASH Trials - Day 1 - AM
Opening Remarks	Jeffrey Siegel, MD Office Director Office of Drug Evaluation Sciences (ODES) Office of New Drugs (OND) Center for Drug Evaluation and Research (CDER) \| FDA
Biomarkers and Surrogate Endpoints	Peter Stein, MD Director OND \| CDER \| FDA
Recent Example of Reasonably Likely Surrogate Endpoint Accepted by the FDA - Reduction in Amyloid Beta Plaques Measured by PET in Alzheimer’s Disease	Kevin Krudys, PhD Associate Director Office of Neuroscience (ON) OND \| CDER \| FDA
Lesson Learned from Makena Drug Development	Christina Chang, MD, MPH Division Director Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine (ORPURM) Division of Urology, Obstetrics and Gynecology (DUOG) OND \| CDER \| FDA
Approval Pathways and NASH/MASH Drug Development	George Makar, MD, MSCE (Acting) Deputy Director Division of Hepatology and Nutrition (DHN) Office of Immunology and Inflammation (OII) OND \| CDER \| FDA
Advancing Endpoint Development	Rebecca Hager, PhD Lead Mathematical Statistician Division of Biometrics III (DBIII) Office of Biostatistics (OB) Office of Translational Sciences (OTS) \| CDER \| FDA
Session Two Introductions	Laura Lee Johnson, PhD Division Director DBIII \| OB \| OTS \| CDER \| FDA
One Stage Reversal of Fibrosis – How Do Hepatologists View This Change?	Don C. Rockey, MD Professor of Medicine Specialties: Gastroenterology and Hepatology College of Medicine Medical University of South Carolina
One Stage Reversal of Fibrosis – How Do Pathologists View This Change?	David E. Kleiner, MD, PhD Senior Research Physician Director, Laboratory Information System Chief, Post-mortem Section Laboratory of Pathology National Cancer Institute (NCI) National Institutes for Health (NIH)
NASH Resolution – How Do Hepatologists View This Change?	Naga Chalasani, MD David W Crabb Professor of Gastroenterology and Hepatology Vice President for Academic Affairs Indiana University School of Medicine & Indiana University Health
NASH Resolution – How Do Pathologists View This Change?	Cynthia Behling, MD, PhD Pathologist University of California, San Diego and Pacific Rim Pathology Lab
The Value of Completing Clinical Benefit Trial for Validating Surrogate Endpoint – Clinician’s View	Theo Heller, MD Section Chief: Translational Hepatology Section, Liver Diseases Branch Senior Investigator: Clinical Research Section, Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases (NIKDDK) National Institute for Health (NIH)
Session Two Q&A Discussion Panel	Naga Chalasani, Laura Lee Johnson, Don C. Rockey, David E. Kleiner, Cynthia Behling, Theo Heller And Scott Friedman, MD Dean for Therapeutic Discovery Fishberg Professor of Medicine Professor of Pharmacologic Sciences Chief, Division of Liver Diseases Icahn School of Medicine at Mount Sinai Mary Rinella, MD Director of the Metabolic and Fatty Liver Program Professor of Medicine at the University of Chicago Pritzker School of Medicine Gregory Levin, PhD Associate Director for Statistical Science and Policy OB \| OTS \| CDER \| FDA
Use of Biomarkers for Diagnosing and Assessing Treatment Response in Noncirrhotic NASH Trials - Day 1 - PM
Session 3 Introductions	George Makar
Alternative Methods for Histologic Assessment	Zachary Goodman, MD, PhD Director, Liver Pathology Research Center for Liver Diseases Inova Fairfax Hospital
Understanding Artificial Intelligence – Promises, Challenges, and Opportunities	Nicholas Petrick, PhD Deputy Director Division of Imaging, Diagnostics, and Software Reliability (DIDSR) Office of Science and Engineering Laboratories (OSEL) Center for Devices and Radiological Health (CDRH) \| FDA
Strengths and Limitations of Artificial Intelligence or Machine Learning – Liver Histology Reading Methods	Cynthia D Guy, MD Professor of Pathology, Liver Pathology Division Chief Department of Pathology, Duke University Health Systems
Session Three Q&A Discussion Panel	George Makar, David Kleiner, Zachary Goodman, Nicholas Petrick, Cynthia Behling, Cynthia Guy And Prakash Jha MD, MPH Medical Officer Division of Molecular Genetics and Pathology OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality (OPEQ) CDRH \| FDA Katy Wack, PhD Vice President, Clinical Development Strategy, PathAI, Inc. Board of Directors, Digital Pathology Association (DPA) Dean Tai, PhD Managing Director & Chief Scientific Officer HistoIndex Pte Ltd
Day One Wrap Up	Frank A. Anania, MD, FACP, AGAF, FAASLD (Acting) Director DHN \| OII \| OND \| CDER \| FDA

Topics & Presentations Day 2	Speakers
Use of Biomarkers for Diagnosing and Assessing Treatment Response in Noncirrhotic NASH Trials - Day 2 - AM
Welcome Remarks, Recap, and Introduction	Insook Kim, PhD Master Scientist Division of Inflammation and Immune Pharmacology (DIIP) Office of Clinical Pharmacology (OCP) OTS \| CDER \| FDA
Biomarkers and Surrogate Endpoints in the Regulatory Framework	Rebecca Hager, PhD Lead Mathematical Statistician DBIII \| OB \| OTS \| CDER \| FDA
Session Two Introductions	Abbas Bandukwala, MS Commander United States Public Health Service (USPHS) Science Policy Analyst Biomarker Qualification Program OND \| CDER \| FDA
Ultrasound Based Liver Stiffness	Philip Newsome MD, PhD, FRCPE Director, Centre for Liver & GI Research University of Birmingham
Magnetic Resonance Elastography (MRE)	Claude Sirlin, MD Professor of Radiology Liver Imaging Group University of California, San Diego
Corrected T1 (cT1) MRI and MRI-PDFF	Scott B. Reeder, MD, PhD Professor and Senior Vice Chair (Research) Chief of Magnetic Resonance Imaging Departments of Radiology, Medical Physics, Biomedical Engineering, Medicine, and Emergency Medicine University of Wisconsin-Madison
Session Two Q&A Discussion Panel	Abbas Bandukwala, Phillip Newsome, Claude Sirlin, Scott Reeder And Daniel Krainak, PhD Assistant Director Division of Radiological Imaging & Radiation Therapy Devices Office of Radiological Health (OHT8) OPEQ \| CDRH \| FDA Rajarshi Banerjee DPhil, MPH, MA, BM BCh, MRCP CEO, Perspectum Ltd Honorary Consultant Physician, Oxford University Hospitals NHS Trust Richard L. Ehman, MD Professor of Radiology Blanche & Richard Erlanger Endowed Professor of Medical Research Mayo Clinic David T. Fetzer, MD Assistant Professor, Abdominal Imaging Division Medical Director, Ultrasound Department of Radiology UT Southwestern Medical Center (UTSW) Céline Fournier, PhD Chief Medical Officer Echosens Lori E Dodd, PhD Mathematical Statistician Clinical Trials Research Section Biostatistics Research Branch Division of Clinical Research NIAID \| National Institutes of Health (NIH)
Use of Biomarkers for Diagnosing and Assessing Treatment Response in Noncirrhotic NASH Trials - Day 2 - PM
Session Three Introductions	Tram Tran, MD, FACG, FAASLD Physician \| Medical Officer DHN \| OII \| OND \| CDER \| FDA
FIB4/APRI Score	Richard K. Sterling, MD, MSc, FACP, FACG, FAASLD, AGAF Professor of Medicine and Chief of Hepatology Chief Clinical Officer, Stravitz-Sanyal Institute for Liver Disease and Metabolic Health Virginia Commonwealth University
ELF Test	Keyur Patel, MD, PhD Professor of Medicine, University of Toronto Staff Hepatologist, UHN Division of Gastroenterology
Session Three Q&A Discussion Panel	Tram Tran, Richard Sterling, Keyur Patel, Insook Kim And Paula V. Caposino, PhD (Acting) Deputy Director Division of Chemistry and Toxicology Devices (DCTD) Office of Health Technology 7 (OHT7) Office of In Vitro Diagnostics OPEQ \| CDRH \| FDA Naim Alkhouri, MD, FAASLD Chief Medical Officer (CMO) Director of the Fatty Liver Program Hepatology, Arizona Liver Health (ALH) Matthew Gee, MSc Director, Regulatory Affairs Siemens Healthcare Diagnostics Inc. Anup Amatya, PhD Division of Biostatistics V (DBV) OB \| OTS \| CDER \| FDA
Session Four Introduction	Frank A. Anania
Using NITs as Diagnostic Biomarkers and to Assess Treatment Response for Noncirrhotic NASH Trials – NIMBLE	Arun J. Sanyal, MBBS, MD Director, Stravitz-Sanyal Institute for Liver Disease and Metabolic Health Professor of Medicine, Physiology, and Molecular Pathology Virginia Commonwealth University School of Medicine
Using NITs as Diagnostic Biomarkers and to Assess Treatment Response for Noncirrhotic NASH Trials – LITMUS	Professor Quentin M. Anstee BSc (Hons), MB BS, PhD, MRCP(UK), FRCP Deputy-Dean of Research & Innovation – Faculty of Medical Sciences Professor of Experimental Hepatology & Consultant Hepatologist Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University
Identify Knowledge Gaps of Circulating NITs (As diagnostic biomarkers and to assess treatment response for noncirrhotic NASH trials)	Mazen Noureddin, MD, MHSc Professor of Medicine at the Lynda K. and David M. Underwood Center for Digestive Disorders J.C. Walter Jr. Transplant Center
Identify Knowledge Gaps of Imaging NITs (As diagnostic biomarkers and to assess treatment response for noncirrhotic NASH trials)	Laurent Castera, MD, PhD Professor of Hepatology, Université Paris Cité Head of the NASH program, Department of Hepatology Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, Clichy, France
Clinical Practice - Use of NITs	Timothy R. Morgan, MD Director, VA National Liver Disease Program Deputy Director, VA National Gastroenterology and Hepatology Program Veterans Health Administration Professor of Medicine, University of California
Session Four Q&A Discussion Panel	Frank A. Anania, Arun J. Sanyal, Quentin M. Anstee, Mazen Noureddin, Laurent Castera, Timothy R. Morgan And Veronica Miller, PhD Director, Forum for Collaborative Research Adjunct Professor, Division of Infectious Diseases and Vaccinology School of Public Health University of California Berkeley Laura Lee Johnson, PhD Division Director DBIII \| OB \| OTS \| CDER \| FDA Vlad Ratziu, MD, PhD Professor of Hepatology, Sorbonne University Institute for Cardiometabolism and Nutrition (ICAN) Paris, France
Day Two Wrap Up	Ruby Mehta, MD Lead Physician DHN \| CDER \| FDA

Agenda

Speaker Biographies

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ABOUT THIS EVENT

FDA is hosting this workshop to update key stakeholders on the state-of-the-art use of biomarkers and noninvasive tests (NITs) based on recent advances in nonalcoholic steatohepatitis (NASH)/metabolic dysfunction associated steatohepatitis (MASH) clinical trials. Drug development for NASH/MASH with liver fibrosis has increased substantially; and there is great interest in developing NITs to detect the presence of fibrosis, and to accurately classify different stages of fibrosis as well as cirrhosis. Candidate NITs include both blood tests (circulating biomarkers) and imaging tests.

In recent years, most data regarding use of NITs have been collected from NASH/MASH clinical trials. However, there are limited published data for use of NITs across the spectrum of the affected population that would be encountered in routine clinical care, including patients without fibrosis.

This workshop will assist the FDA in identifying current knowledge gaps for using NITs as diagnostic biomarkers and reasonably likely surrogates, as well as provide a framework for additional data that are needed to fill these knowledge gaps. Ultimately, the FDA seeks to learn whether expert stakeholders have evidence to indicate currently available NITs are adequate to meet the Agency evidentiary standard for assessing primary evidence of clinical efficacy.

The primary focus of this workshop is “non-cirrhotic NASH/MASH population with advanced (i.e., Stage 2 or Stage 3) liver fibrosis”. The workshop will not address the use of biomarkers for treatment trials in cirrhosis due to NASH/MASH, however, the workshop will discuss identification of “progression to cirrhosis” using biomarkers.

INTENDED AUDIENCE

Stakeholders in NASH clinical trials, including clinicians, clinical trial investigators, industry, regulators, and patients.

OBJECTIVES

Review the currently accepted surrogate endpoints for NASH/MASH marketing trials
Emphasize the importance of completing clinical benefit trials both to fulfill regulatory requirements for full traditional drug approval and to validate biomarkers
Investigate new techniques to assist in interpretation of histopathology – artificial intelligence-based reads - its strengths and limitations
Review the current data supporting the use of NITs as “diagnostic biomarkers”
Review the current data supporting the use of NITs as biomarkers of “treatment response”
Summarize current use of NITs in clinical practice
Stimulate further investigations for NIT use in NASH/MASH clinical trials

FDA RESOURCES

Guidance for Industry: Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis: Developing Drugs for Treatment

Event Materials

Title	File Type/Size
Speaker Biographies - Use of Biomarkers for Diagnosing and Assessing Treatment Response in Noncirrhotic NASH Trials	pdf (344.66 KB)