Non-Invasive Biomarkers of Metabolic Liver Disease (NIMBLE)

Non-alcoholic steatohepatitis (NASH) has been estimated to affect between 9 and 15 million people in the United States. A serious condition associated with obesity and diabetes, NASH causes fat to build 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 options for the patient. If left untreated, it can lead to permanent liver damage, which ultimately requires liver transplant to prevent cancer or death. Currently, the only means of diagnosing NASH is by visual analysis of a liver biopsy. Surgical biopsy is an invasive, expensive, and painful procedure that carries risk of serious complications. In addition, it provides information from only a small part of the liver and may not present an accurate picture. As there are no obvious symptoms early in the disease, and a difficult and expensive process is required for diagnosis, patients with NASH often do not get identified until it is too late, and they have developed cirrhosis or liver cancer. Drug development effort in this space has also been hampered as recruitment to a clinical trial and assessment of response to treatment requires a liver biopsy. To properly treat these patients and develop effective drug therapies for them, non-invasive and reliable measures of NASH in at-risk patients must be found.

Several companies have developed blood-based and imaging-based biomarkers to measure liver health, but these technologies haven’t been compared systematically with each other or validated against the gold standard of liver biopsy screening.

The Biomarkers Consortium Non-Invasive Biomarkers of Metabolic Liver Disease (NIMBLE) has reviewed currently available biomarkers for NASH to identify those with sufficient data to justify further validation. The candidate markers will be studied systematically to assess their performance as compared to the gold standard and their suitability to be implemented widely—perhaps eventually instead of the biopsy. Selected biomarkers (whether serum/plasma-based, imaging-based or a combination thereof) will be tested in a prospective clinical trial to compare their performance against liver biopsies as well as their ability to measure response to treatment.

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

  1. Diagnose and stage the disease and;
  2. Measure response to therapeutic intervention.

Goals

  • Standardize and validate a set of non-invasive biomarkers (circulating, functional and/or imaging) for the diagnosis and staging of NASH. The team will also assess the markers for identification of individuals at risk of progression to cirrhosis and/or in need of pharmacological 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 use in clinical trials to develop therapies for NASH as well as to diagnose NASH and assess response to treatment in the clinic.

Results & Accomplishments

Media

FNIH Announcement (June 11, 2019): FNIH Biomarkers Consortium Launches NIMBLE to Replace Invasive and Painful Biopsy with Non-Invasive Biomarkers for Liver Disease

Partners

Public-Sector Partners:
U.S. Food and Drug Administration (FDA)

Private-Sector Partners:
Allergan*
AstraZeneca*
Boehringer-Ingelheim*
Bristol-Myers Squibb*
Echosens SA*
GE Healthcare*
Genentech, a member of the Roche Group*
Gilead Sciences, Inc.*
Intercept Pharmaceuticals, Inc.*
Novo Nordisk*
Pfizer Inc*
Takeda Pharmaceutical Company Limited*

Academic Partners:
Massachusettes General Hospital, an affiliated teaching hospital of Harvard Medical School
University of California San Diego School of Medicine
Virginia Commonwealth University

*Provided financial or in-kind support for this program.

Click here to read what project partners are saying.

FNIH Contact

Tania Kamphaus, Ph.D., Scientific Program Manager, Metabolic Disorders, tkamphaus@fnih.org