Novel Technology to Power a Blood-Based Test for NASH
Nonalcoholic steatohepatitis (NASH) remains largely underdiagnosed, as it carries no obvious symptoms in its early stages, and also because of the lack of widely available non-invasive tests specifically developed to diagnose the disease. The underdiagnosis of NASH represents a major unmet need, and is a barrier for identification of patients at higher risk for disease progression, who would be eligible for therapeutic intervention.
As part of our strategy to address this unmet need in NASH, we have invested in a research and development program with the objective of identifying specific biomarkers that are expressed at different levels in patients with NASH and fibrosis (F) >2. This program consists of a multi-year effort that led to the development of NIS4™, a novel technology to support a non-invasive test specifically designed to identify patients with at-risk NASH (NAS ≥4 and F ≥2) in populations with metabolic risk factors, who are at a higher risk for adverse clinical outcomes and who may be appropriate candidates for therapeutic intervention.
Multiple NASH histological features are associated with long-term outcomes and collectively define the patient who is at greater risk for progression: presence of NASH (with a NAS ≥4) and fibrosis stage (F ≥2) are associated with clinical outcomes and mortality.7, 8,9,10 Our development program included the statistical analysis of >100 biomarkers tested in the blood of untreated patients within the course of the elafibranor GOLDEN-505 (Phase 2b) and RESOLVE-IT™ (Phase 3) clinical trials . This research led to the identification of four independent, NASH-related biomarkers that yielded the best overall diagnostic performance to identify patients with at-risk NASH (NAS ≥4 and F≥2) in patient cohorts in these studies: 1) miR-34a (steatosis/inflammation/hepatocyte ballooning marker), 2) alpha-2 macroglobulin (fibrosis marker), 3) YKL-40 (fibrosis marker) and 4) HbA1c (metabolic/insulin resistance marker).6
NIS4™ is a multianalyte technology that enables quantitative measurement of these biomarkers and combines the results through a single proprietary GENFIT algorithm to produce a single score that identifies at-risk NASH in patients with metabolic risk factors.6 These patients are at higher risk for adverse clinical outcomes and therefore may be considered for additional diagnostic evaluation and/or therapeutic intervention, agnostic to the specific intervention.5,11 Unlike other currently available non-invasive diagnostic approaches for NASH, NIS4™ technology is the foundation for the development of a diagnostic test to assess both NASH activity and fibrosis.6
In order to validate its clinical diagnostic performance, we tested NIS4™ technology in independent patient cohorts. In this assessment, NIS4™ technology demonstrated a robust diagnostic performance across clinically relevant subpopulations, which was not influenced by nor dependent on patients’ gender, body mass index (BMI), transaminase levels or metabolic co-morbidities as compared to other diagnostic approaches.8
As the foundation for the development of a non-invasive diagnostic aid to rule in and/or rule out at-risk NASH in populations with metabolic risk factors, NIS4™ technology has the potential to improve clinical care by being deployed within the framework of clinical laboratories, and to reduce the need for liver biopsies.
In January 2019, we took a first step toward making NIS4™ technology available for use in clinical research by signing a license agreement with LabCorp to enable its Covance subsidiary, a leading clinical laboratory and end-to-end drug development company, to internally develop, market and deploy a test utilizing NIS4™ technology. Covance made the test available in November 2019 for exploratory use within the scope of NAFLD/NASH clinical research/trials.
In order to make a NIS4™ technology available commercially on a large scale, in September 2020 GENFIT signed a licensing agreement to enable LabCorp to develop and commercialize a blood-based molecular diagnostic test powered by NIS4™ technology throughout the U.S. and Canada, allowing for widespread access to a diagnostic test based on the technology for healthcare providers.
We plan to use these benefits to further support our ultimate goal, which is to seek regulatory approval of our own NIS4™-based in vitro diagnostic test to enable its widespread availability as the first FDA-approved and CE-marked blood-based diagnostic to identify at-risk NASH.
We believe that broad adoption of our NIS4™ proprietary multianalyte testing technology, when available for use as a clinical diagnostic, will provide healthcare providers with a tool for the non-invasive identification of patients with at-risk NASH in populations with metabolic co-morbidities, who may benefit from therapeutic intervention or additional diagnostic evaluation.