Phase three clinical trials in idiopathic pulmonary fibrosis

ABSTRACT Introduction The last two decades witnessed an increasing number of well-designed late phase trials in patients with Idiopathic Pulmonary Fibrosis (IPF), leading to the approval of the first effective therapies for these patients, pirfenidone and nintedanib. Currently, novel putative agents for the treatment of IPF are being tested in phase III trials, possibly marking a new breakthrough in IPF management. Areas covered In this review, the available evidence on completed phase III trials in IPF is summarized, from the past failures of immunosuppressive and anti-inflammatory agents, anticoagulants and endothelin-receptor antagonists to the positive results of the antifibrotic treatments that revolutionized IPF therapeutic landscape. Literature search was performed using Medline and Clinicaltrials.org databases (1999–2020). Expert opinion In the relatively young history of pharmaceutical research in IPF, most phase III trials provided disappointing results, however the lessons learned helped paving the way to the success of the first therapies capable of modifying the natural history of this deadly disease. To date, the conduction of robustly designed phase III trials on novel drugs remains crucial to pursue the goal of halting disease progression in these patients, using a therapeutic approach that should become more and more tailored to the individual.