Non-Invasive Biomarkers of Metabolic Liver Disease (NIMBLE)

Revolutionizing the ability to diagnose, monitor and treat metabolic liver disease

The Problem
Patients at risk of developing non-alcoholic steatohepatitis (NASH) do not present with symptoms until the disease has advanced to a dangerously late stage, and the only current way to diagnose NASH early is by invasive biopsy.
The Solution
The NIMBLE Project will explore the ability of various non-invasive biomarkers to diagnose pre-symptomatic NASH, characterize progression of the disease, predict patients’ risk of developing complications and assess response to treatments.

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.

Partners

Public-Sector Partners

  • U.S. Food and Drug Administration (FDA)

Private-Sector Partners

  • AbbVie*
  • AstraZeneca*
  • Boehringer-Ingelheim*
  • Bristol-Myers Squibb*
  • Echosens SA*
  • GE Healthcare*
  • Genentech, a member of the Roche Group*
  • Gilead Sciences, Inc.*
  • Global Liver Institute
  • Intercept Pharmaceuticals, Inc.*
  • Novo Nordisk*
  • Pfizer Inc*
  • Takeda Pharmaceutical Company Limited*

Academic Partners

  • Massachusetts 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

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

  • FDA Letter of Intent Accepted for circulating markers.

    • The FDA has accepted the NIMBLE LOI. Read here.

Media

  • FNIH Announcement (May 15, 2020): FNIH Biomarkers Consortium NIMBLE Project Receives FDA Nod to Move Forward in Biomarker Qualification Read more
  • Diagnostics World (July 25, 2019): NIMBLE Could Make Liver Biopsy for Diagnosing NASH Obsolete Read more
  • FNIH Announcement (June 11, 2019): FNIH Biomarkers Consortium Launches NIMBLE to Replace Invasive and Painful Biopsy with Non-Invasive Biomarkers for Liver Disease Read more