Shedding light on developmental drugs for idiopathic pulmonary fibrosis

ABSTRACT

Introduction

Idiopathic pulmonary fibrosis (IPF) is an age-related disease of unknown cause. The disease is characterized by relentless scarring of the lung parenchyma resulting in respiratory failure and death. Two antifibrotic drugs (pirfenidone and nintedanib) are approved for the treatment of IPF worldwide, but they do not offer a cure and are associated with tolerability issues. Owing to its high unmet medical need, IPF is an area of dynamic research activity.

Areas covered

There is a growing portfolio of novel therapies that target different pathways involved in the complex pathogenesis of IPF. In this review, we discuss the mechanisms of action and available data for compounds in the most advanced stages of clinical development. We searched PubMed for articles on this topic published from 1 January 2000, to 6 June 2020.

Expert opinion

The approval of pirfenidone and nintedanib has fueled IPF drug discovery and development. New drugs are likely to reach the clinic in the near future. However, numerous challenges remain; the lack of animal models that reproduce the complexity of human disease and the poor translation of preclinical and early-phase positive effects to late stage clinical trials must be tackled.

KEYWORDS:

• Idiopathic pulmonary fibrosis
• novel drugs
• therapy
• clinical trials
• treatment

Article highlights

• Idiopathic pulmonary fibrosis (IPF) is an age-related lung disease of unknown cause and is characterized by progressive and irreversible scarring of the lung and loss of function.

• Current therapies can reduce the rate of lung functional decline but do not halt the relentless accumulation of scar tissue. The unmet need for novel therapies remains very high.

• Numerous promising drugs with diverse molecular properties and mechanisms of action are being developed. Some are likely to reach the clinic in the near future.

• Challenges for future drug discovery and development include the lack of animal models that recapitulate the complexity of human disease and the poor translation of pre-clinical and early-phase positive effects to late stage clinical trials.

This box summarizes key points contained in the article.

Declaration of interest

P Spagnolo reports personal fees and institutional grants from PPM Services, Boehringer-Ingelheim and Roche, and personal fees from Chiesi and Galapagos. F Bonella reports personal fees and nonfinancial support from Boehringer-Ingelheim, Roche and Savara Pharma. CJ Ryerson reports grant funding, consulting fees and speaking honoraria from Roche and Boehringer-Ingelheim. A Tzouvelekis reports travel support, speaking honoraria or consulting fees from Boehringer-Ingelheim, Roche, Elpen, Chiesi and Astra Zeneca. TM Maher reports research funding and/or consulting fees or other remuneration from GSK, UCB, Boehringer-Ingelheim, Astra Zeneca, Roche, Bayer, Biogen, Cipla, Prometic and Sanumed, and has stock options or bond holdings in the for-profit corporation Apellis. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.