Forum Focus: Methods of utilizing the NASH Patient Access and Screening Strategies (NASH PASS®) database for biomarker and translational research
On November 18, 2021, the NASH Roundtable™ and ProSciento, Inc. hosted the 4th Annual NASH Roundtable™ Virtual Forum, with co-hosts Antaros Medical AB and Nordic Bioscience A/S. The NASH Roundtable™ Forum is held twice a year, bringing together leading hepatologists, endocrinologists, and clinical development experts from around the world to discuss advances in the science, clinical research, and therapeutics for nonalcoholic fatty liver disease, steatohepatitis (NAFLD/NASH) and related metabolic diseases.
Moderating the event were NASH Roundtable™ co-chairs: Dr. Marcus Hompesch, President and Chief Executive Officer of ProSciento, Inc.; Dr. Rohit Loomba, Professor of Medicine and Director of Hepatology at the University of California San Diego; and Dr. Arun Sanyal, Professor of Medicine at Virginia Commonwealth University School of Medicine.
Presenters included Dr. Arun J. Sanyal; Dr. Julio Gutierrez, Vice President of Clinical Research and Clinical Science of ProSciento, Inc. and Transplant Hepatologist at Scripps Health; Dr. Morten Karsdal, Chief Executive Officer of Nordic Bioscience A/S; and Dr. Lars Johansson, Chief Scientific Officer of Antaros Medical AB.
Presentation topics included methods of utilizing the NASH Patient Access and Screening Strategies (NASH PASS®) database and biobank for biomarker and translational research; identifying critical biomarkers for liver fibrosis; advances in imaging technologies; and the various collaborative opportunities available with NASH PASS.
NASH PASS is a clinical research platform consisting of a database of clinical data and biobank from subjects identified as high risk for NAFLD/NASH. The data include demographics, blood work, as well as FibroScan and biopsy data from over 3,000 subjects. In addition, the NASH PASS clinical site network allows for efficient recruitment of subjects with NAFLD/NASH risk phenotypes. Given the depth and breadth of the data, as well as the flexibility and efficiency of subject recruitment, NASH PASS provides valuable opportunities for:
- Researchers interested in biomarker discovery and validation, endpoint determination, and the study of NAFLD/NASH as a multi-system disorder.
- Healthcare providers and clinical trial sites by providing the tools, methodology, and support to diagnose and monitor at-risk patients for the progression of NAFLD/NASH.
- Principal investigators and diagnosed patients interested in participating in clinical trials investigating new NASH drug candidates and other clinical interventions.
- Biopharma companies working with ProSciento to substantially improve patient access and enrollment and streamlining site selection for NASH clinical trials, as well as optimization of inclusion-exclusion (I/E) criteria.
Utilizing NASH PASS® Biobank for Biomarker Discovery and Translational Research
Presentation by Julio Gutierrez, M.D., Vice President of Clinical Research and Clinical Science, ProSciento, Inc., and Transplant Hepatologist at Scripps Health
Dr. Gutierrez’ presentation focuses on NASH PASS as a highly effective collaborative research tool. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are major public health challenges, and approximately 24 percent of the U.S. population will develop NAFLD. Despite NASH being highly prevalent, drug development may be delayed because of a lack of suitable subjects enrolling in clinical trials. Rates of clinical trial enrollment have been steadily dropping since 2009, and access to individuals who meet the phenotype of NASH patients in the U.S. is limited.
Conclusion: NASH PASS gives at-risk communities access to research. EMR data is used to prescreen subjects, and it utilizes proprietary algorithms to identify subjects with NAFLD and those with the highest risk of NASH. As a result of the optimized screening and recruitment efforts, there is an abundance of data and biological specimens.
As a highly adaptable platform utilized at any stage, the recruitment methodology for NASH PASS is robust, and currently includes custom technology, as well as physician-to-patient, physician-to-physician, and patient-to-patient referral programs. These efforts feed into the top of the funnel of the recruitment science process, including keeping patients engaged. Data from the first 3,000 NASH PASS subjects that was presented at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting was also reviewed during Dr. Gutierrez’ presentation.
ProSciento’s initiative for 2022 is the development of a polygenic risk model for NASH, and it currently has a tool for phenotyping patients at high risk for metabolic disease. ProSciento is pursuing addtional collaborations on the scientific side.
Biomarkers of Hepatic Fibrosis, Fibrogenesis, and Fibrosis Resolution
Presentation by Morten Karsdal, Ph.D., Chief Executive Officer, Nordic Bioscience A/S
Dr. Karsdal discusses how liver fibrosis is a multi-organ disease, and extracellular matrix remodeling is the common denominator in all chronic diseases. He poses the question, “How do we find patients who are progressing fast?” The answer: biomarkers of fibrosis – we need to develop a set of solutions with the liver at the center.
Conclusion: Collagen fragments are key elements of this solution set because collagen is part of all organs and is central for tissue structure and function. When tissue modeling, the balance of tissue formation and degradation is central to most pathologies. Collagen fragments can predict death and response to treatment, as well as inform on early efficacy of clinical interventions. NASH PASS provides a platform to help understand the structure of organs and better profile patients and Dr. Karsdal highlighted the current collaboration between NASH PASS and Nordic Biosciences.
Advances in Imaging Technologies for Fibrotic Diseases – A Look Forward
Presentation by Lars Johansson, Ph.D., Chief Scientific Officer, Antaros Medical AB
Dr. Johansson’s presentation centers around imaging and how it can help evaluate the effect of medications on different parts of the disease development. The use of PET and MRI imaging were discussed in detail. These imaging modalities can determine hepatocyte density and function. Though this technology has existed for some time, functional liver MRI using gadoxetic acid is an important development to help predict risk in cirrhotic patients.
Conclusion: Clinicians should use a holistic approach using advanced imaging to understand treatment effects in fibrosis, cirrhosis, and portal hypertension by integrating imaging of liver structure and composition, liver function, ascites, liver stiffness, spleen stiffness, fibrogenesis, spleen structure and composition, and hemodynamics. These can be all integrated into a single exam to understand disease stage and progression. Combining metabolic and anti-fibrotic treatments is being tested by several companies. With imaging, we can assess the early effects of drug treatment on lowering the liver fat and improving insulin resistance, as well as downregulation of fibrogenesis and effects on fibrosis.
Collaborative Translational Research Opportunities Utilizing the NASH PASS® Biobank
Presentation by Arun J. Sanyal, M.D., Professor, Division of Gastroenterology, Hepatology and Nutrition, at Virginia Commonwealth University School of Medicine
Dr. Sanyal’s session focuses on NASH not only as a liver disease, but part of a multi-system disorder since, in most cases, approximately 70 to 85 percent of patients have one or more comorbidity. Key elements in non-invasive test (NIT) development include biological plausibility, analytical performance, clinical validity, clinical utility, and evaluating benefit versus harm. There are significant gaps in the field that need to be addressed to improve analytical performance. Dr. Sanyal also discusses the various perspectives by multiple stakeholders, which requires a strategic approach to meet everyone’s needs, including clinician, regulator, and payor.
Also discussed are the parameters and results of the FNIH NIMBLE study2 of circulating biomarkers for NASH and activity and fibrosis stages. These data allow for the opportunity to analyze population results in more granular detail. The world of NIT has made progress in allowing information and data to be analyzed, especially when compared and paired with LITMUS3.
Conclusion: How can we bring all these data together? One powerful approach is to use the NASH PASS platform to help expedite clinical research and help move the field forward.
NASH Roundtable™ Members that participated in the discussion portion of this year’s forum included Dr. Elisabetta Bugianesi, Professor of Gastroenterology, School Medicine at the University of Torino, Italy; Dr. Scott Friedman, Dean, Therapeutic Discovery and Chief, Division of Liver Diseases, at Icahn School of Medicine at Mount Sinai; Dr. Eric Lawitz, Vice President, Scientific and Research Dev, Texas Liver Institute, and Clinical Prof of Medicine, University of Texas Health San Antonio; Dr. Vlad Ratziu, Professor of Hepatology at Sorbonne Université and Pitié-Salpêtrière Hospital; Dr. Manuel Romero-Gómez, Professor at University of Seville and Director of Digestive, Liver and Inflammatory Diseases Program at Institute of Biomedicine of Seville; Dr. Detlef Schuppan, Professor, Hepatology & Gastroenterology at Mainz University & Beth Israel Medical Center, Harvard; and Dr. Miriam Vos, Assistant Professor, Pediatrics, Hepatology at Emory and Director, Pediatric Fatty Liver at Children’s Healthcare of Atlanta.
If you have any questions about the NASH Roundtable™ or the forums held twice a year, please contact firstname.lastname@example.org.
1Arshad. Curr. Pharm Des. 2020:26(1):993-997
2 Non-Invasive Biomarkers of Metabolic Liver Disease (NIMBLE). The Foundation for the National Institutes of Health.
3 LITMUS: Progress towards diagnosing and better treating liver disease. EASL.