Pamrevlumab for the treatment of idiopathic pulmonary fibrosis

ABSTRACT

Introduction

The two available therapies for idiopathic pulmonary fibrosis (IPF), pirfenidone and nintedanib, slow down but do not halt IPF progression. As such, in the last few years several agents with specific molecular targets have been investigated to find a cure forIPF. Pamrevlumab, a recombinant human antibody that binds to connective tissue growth factor (CTGF) has emerged as a potential therapy for IPF and has advanced to phase 3 clinical trials.

Areas covered

The authors offer a backdrop to the current IPF treatment market and describe the chemistry, pharmacokinetics and pharmacodynamics of pamrevlumab. They summarize the preclinical and early clinical evidence on pamrevlumab and propose ways of progressing this agent further as a potential IPF treatment.

Expert opinion

Pamrevlumab was effective and safe in patients in a placebo-controlled phase 2 trial, demonstrating its potential to become an alternative therapeutic option for IPF; however, the feasibility of intravenous administration in clinical practice may be a hurdle to its use as a first-line treatment. Further studies are necessary to assess its effects when administered with pirfenidone or nintedanib and this could open up a new era of combined therapeutic approaches for IPF.

KEYWORDS:

• Idiopathic pulmonary fibrosis
• pamrevlumab
• FG-3019
• anti-CTGF
• randomized clinical trial

Article highlights

• The currently available antifibrotic treatments for IPF, nintedanib and pirfenidone, slow down, but do not stop IPF progression in patients.

• Connective tissue growth factor (CTGF) is a glycoprotein thought to interact with regulatory modulators such as transforming growth factor-β (TGF- β); this elicits cellular responses, for example, production of extracellular matrix, motility and adhesion, and biological activities associated with tumorigenesis and aberrant tissue repair.

• Pamrevlumab is a fully human recombinant antibody that recognizes and binds to connective tissue growth factor (CTGF) and prevents it from activating downstream profibrotic signaling.

• In a recent randomized, placebo-controlled phase 2 trial in IPF patients, intravenously administered pamrevlumab showed optimal tolerability and comparable efficacy to current antifibrotics in terms of reducing functional decline. It demonstrated reduction of the progression of fibrotic changes on high resolution CT scan.

• If these encouraging results are confirmed in the ongoing phase 3 trial, pamrevlumab may become a valid therapeutic option alongside pirfenidone and nintedanib for patients with IPF.

This box summarizes key points contained in the article.

Declaration of interest

G Sgalla reports personal fees from Boehringer Ingelheim, outside the submitted work. 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. 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.