Abstract

The session aim is “…to discuss how appropriate, well validated, biomarkers will drive a reduction in drug attrition in all therapeutic areas over the next few decades.” One area with high attrition has been fibrosis, in part due to poor predictivity, and/or inappropriate use, of animal models. For example, over the past decade there have been over 20 failures in late stage clinical trials despite preclinical studies suggesting efficacy of novel compounds in the bleomycin “model” of idiopathic pulmonary fibrosis (IPF). Only 2 agents, pirfenidone and nintedanib, are approved and progression of these agents as anti-fibrotics. Approval of these was largely serendipitous, rather than driven from a primary hypothesis and delivered through a focused translational strategy. Five years on from widespread approval of pirfenidone and nintedanib, there are 3 compounds in PhIII development in IPF and a further wave in PhII. However, compound progression has predominantly been based on lung function measurements rather than through use of predictive biomarkers. In non-alcoholic steatohepatitis (NASH) there are no approved anti-fibrotic agents and de-risking compound progression remains largely dependent on histological readouts from liver biopsies. Can advances in biomarkers of fibrosis support earlier and improved clinical decision making, and increase the probability of bringing effective medicines to patients?