Drug discovery and development in idiopathic pulmonary fibrosis: challenges and opportunities

•There is an unmet medical need for new therapies to treat IPF.•The profile of the two approved drugs, nintedanib and pirfenidone, makes developing new drugs challenging.•Most new therapies will need to have additive benefit in combination with the approved therapies.•Existing assays and models for lung fibrosis are not predictive of clinical efficacy.•New pre-clinical and clinical strategies are both needed to facilitate drug R&D. Idiopathic pulmonary fibrosis (IPF) is an area of high unmet clinical need and of high research activity for the pharmaceutical and biotech industries. The two approved therapies, nintedanib and pirfenidone, have efficacy and tolerability issues. These have impacted their use and opened the need to develop new therapeutics. The strategies for developing these are, in part, being shaped by existing therapies, and several challenges to drug discovery and development have emerged since their approval. These range from the need for better translational preclinical models to derisk new targets and to guide clinical trial design, to the need to design effective clinical studies to evaluate new compounds as adjunct to existing or stand-alone therapies. In this review, we highlight the research and development (R&D) challenges and opportunities in this therapy area. The pharmacological and adverse effect profiles of the two approved therapies for IPF make the development of new therapies challenging. Considering the similarity of the characteristics of drug candidates to Standard of Care is important in defining positioning and development strategies for this disease.