Non-invasive prognostic and predictive biomarkers offer a promising solution to this hurdle, as they capably identify patient subgroups which can be used for stratification or enrichment in drug development trials. Identifying cut-off points is a prerequisite for both biomarker types, with prognostic tools signalling that a patient is at risk of an outcome, and predictive ones identifying patients more likely to receive benefits or experience risk from a given intervention.
This article details the lessons learned from interactions between ‘Liver Investigation: Testing Marker Utility in Steatohepatitis’ (LITMUS) and health authorities in the EU (EMA) and the US (FDA). Its primary focus is NAFLD and NASH biomarker development.
Panel discussions identified diagnostic screening and prognostic enrichment as the biomarker categories with the highest chance of clinical success. Biomarkers with predictive and/or prognostic power would theoretically expedite the drug development process by acting as surrogate endpoints, after which trials must be continued to validate an intervention’s impact on liver-related outcomes. If it is to be used in a singular therapeutic trial, the biomarker approval process in the United States requires IND, NDA and BLA submissions. Conversely, for multiple drug development initiatives, a biomarker is validated via the Biomarker Qualification Program, which qualifies the analyte itself and not the method used to measure it. Providing a biomarker’s technical performance data in cohorts representative of the intended use population is pivotal to this process, as it testifies to the tool’s reproducibility and, thus, its reliability. Crucially, the Biomarker Qualification Program’s rigour means interdisciplinary panels of experts (e.g., clinical, technical, and regulatory) and stakeholders are essential to biomarker approval.