Treatment of idiopathic pulmonary fibrosis: an update on emerging drugs in phase II & III clinical trials

ABSTRACT

Introduction

Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating lung disease with poor prognosis. Although two antifibrotics have been approved in the past decade there are no curative therapies.

Areas covered

This review highlights the current landscape of IPF research in the development of novel compounds for the treatment of IPF while also evaluating repurposed medications and their role in the management of IPF. The literature search includes studies found on PubMed, conference abstracts, and press releases until March 2024.

Expert opinion

Disease progression in IPF is driven by a dysregulated cycle of microinjury, aberrant wound healing, and propagating fibrosis. Current drug development focuses on attenuating fibrotic responses via multiple pathways. Phosphodiesterase 4 inhibitors (PDE4i), lysophosphatidic acid (LPA) antagonists, dual-selective inhibitor of αvβ6 and αvβ1 integrins, and the prostacyclin agonist Treprostinil have had supportive phase II clinical trial results in slowing decline in forced vital capacity (FVC) in IPF. Barriers to drug development specific to IPF include the lack of a rodent model that mimics IPF pathology, the nascent understanding of the role of genetics affecting development of IPF and response to treatment, and the lack of a validated biomarker to monitor therapeutic response in patients with IPF. Successful treatment of IPF will likely include a multi-targeted approach anchored in precision medicine.

KEYWORDS:

• idiopathic pulmonary fibrosis
• LPA antagonist
• PDE4 inhibitor
• treprostinil
• αvβ6 integrin blockade

Article highlights

• LPAR antagonists and integrin αVβ1αVβ6 blockers are novel molecules targeting IPF.

• PDE4B inhibition reduces fibrogenesis while limiting PDE4 inhibitor related side effects.

• Repurposing drugs such as Treprostinil to treat IPF expedites clinical trials.

• IPF therapeutics will benefit from precision medicine focusing on biomarkers and genetics.

Declaration of interest

S. MacIsaac received educational grants and speaker honoraria from Boerhinger Ingelheim. Educational grant from Janssen

D. Somboonviboon received honoraria for lectures from Boehringer Ingelheim (Thai) Ltd.

C. Scallan received research support and consulting and speaking fees from Boehringer Ingelheim. He also receives research support from SeamlessMD, the Juravinski Research Institute, the Canadian Pulmonary Fibrosis Foundation, and the Ontario Centre of Innovation.

M. XKolb- reports grants from Canadian Institute for Health Research, Boehringer Ingelheim, United Therapeutics, Structure Therapeutics; personal fees from Boehringer Ingelheim, Roche, European Respiratory Journal, LabCorp, Bellerophon, United Therapeutics, Nitto Denko, Pieris, Abbvie, Avalyn, DevPro Biopharma, Horizon, Algernon, CSL Behring, AZ, Sanofi, Structure Therapeutics and Cipla.

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.