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.

KEYWORDS:

• Idiopathic pulmonary fibrosis
• phase 3 clinical trials
• rcts
• nintedanib
• pirfenidone

Article highlights

• The therapeutic scenario of Idiopathic Pulmonary Fibrosis (IPF) was completely reshaped over the last two decades thanks to an increasing number of well-designed phase III randomized clinical trials.

• • Pirfenidone and nintedanib proved to be equally effective treatments for slowing down the functional decline in these patients, and represents the only approved treatment options for IPF.

• • Novel agents including pamrevlumab (an anti-CTGF antibody), pentraxin-2 and GLPG −1690 (an autotaxin inhibitor), have recently shown promising efficacy in IPF and are currently being investigated in phase III trials.

• • Future trials in IPF will have to face important challenges, including the adoption of appropriate disease stratification and the choice of appropriate endpoints to maximize trial effectiveness and answer the need for a more tailored therapeutic approach.

Declaration of interest

L Richeldi has received grants and personal fees from Boehringer Ingelheim and InterMune, and personal fees from Biogen-Idec, ImmuneWorks, Medimmune, Roche, Sanofi-Aventis, Shionogi, and Takeda outside of the submitted work. G Sgalla reports personal fees from Boehringer Ingelheim outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.