Non-Invasive Biomarkers of Metabolic Liver Disease (NIMBLE)

Overview

Non-alcoholic steatohepatitis (NASH), a serious condition associated with obesity and diabetes, is estimated to affect between 9 and 15 million people in the United States. NASH causes fat to accumulate in the liver, which leads to inflammation and cell damage. Unfortunately, NASH does not present any symptoms until it has progressed into later stages, when serious complications like cirrhosis leave few treatment options for patients. Because diagnosing early-stage NASH is difficult and expensive, patients with NASH often remain undiagnosed until it is too late and they have developed either cirrhosis, which ultimately requires liver transplant, or liver cancer, which can be fatal. Currently, the only means of diagnosing NASH is by visual imaging analysis of a liver biopsy. However, surgical biopsy—an invasive, expensive, and painful procedure that carries risk of serious complications—only provides information from a small part of the liver and may not present an accurate picture of a patient’s disease. Drug development efforts against NASH have been hampered by the fact that recruitment into a clinical trial and assessment of treatment response require that patients undergo a liver biopsy. To properly treat these patients and to develop effective therapies against NASH, researchers must produce new, non-invasive and reliable measures of NASH in at-risk patients.

Several companies have developed blood-based and imaging-based biomarkers to measure liver health, but these technologies have neither been systematically compared nor validated against the current gold standard of liver biopsy screening.

The Biomarkers Consortium Non-Invasive Biomarkers of Metabolic Liver Disease (NIMBLE) has reviewed currently available NASH biomarkers to identify those with sufficiently promising data to justify further validation. NIMBLE will systematically study these candidate biomarkers to assess their performance as compared to the gold standard and to evaluate their suitability for wider implementation in clinical trials, perhaps eventually replacing liver biopsy. NIMBLE will test selected biomarkers, whether they be serum/plasma-based, imaging-based, or a combination thereof, in a prospective clinical trial to compare their performances against liver biopsy and to test their ability to measure treatment responses.

The NIMBLE Project is a comprehensive, five-year collaborative effort to standardize, compare and appropriately validate these imaging and circulating biomarkers to:

1. Diagnose NASH and assess patients’ stage of disease.
2. Measure responses to therapeutic interventions.

Goals

• Standardize and validate a set of non-invasive biomarkers (circulating, functional, and/or imaging) for the diagnosis and staging of NASH.
• Assess these biomarkers for the ability to identify individuals at risk of progression to cirrhosis and/or in need of pharmacologic or non-pharmacologic intervention.
• Standardize and advance validation of a set of non-invasive biomarkers (circulating, functional, and/or imaging) to assess response to therapeutic intervention in subjects with NASH.

If successfully qualified by regulatory authorities, the selected NASH biomarkers will be used in clinical trials to develop therapies against NASH as well as to diagnose NASH and assess patients’ responses to treatment in the clinic.

Results & Accomplishments

• Primary Results: NIMBLE Abstract from AASLD Meeting, Nov 2021.
• FDA Letter of Intent Accepted for NIMBLE Circulating Markers.
• FDA Letter of Intent Accepted for NIMBLE Imaging.

Publications

• Arun J. Sanyal, Sudha S. Shankar, Roberto A. Calle , Anthony E. Samir, Claude B. Sirlin, Sarah P. Sherlock, Rohit Loomba , Kathryn J. Fowler, Clayton A. Dehn, Helen Heymann and Tania N. Kamphaus. Non-Invasive Biomarkers of Nonalcoholic Steatohepatitis: the FNIH NIMBLE project. Nature Medicine. February 20, 2022. https://doi.org/10.1038/s41591-021-01652-8