Reducing lung function decline in patients with idiopathic pulmonary fibrosis: potential of nintedanib

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic lung disease with no clear etiology and a paucity of therapeutic options. Nintedanib (previously known as BIBF 1120) is a tyrosine kinase receptor antagonist which inhibits a number of key receptors, including those for platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF). These growth factors are profibrotic and each has been investigated as a potential standalone therapeutic target in IPF. Simultaneous inhibition of these receptors, with an analog of nintedanib, has proved to be effective in experimental animal models of pulmonary fibrosis. This observation, together with extensive safety and pharmacokinetic data from studies of nintedanib in malignancy, paved the way for the clinical development of this drug in IPF. The Phase IIb TOMORROW trial demonstrated that treatment with nintedanib may potentially slow decline in lung function, decrease the frequency of acute exacerbations, and improve quality of life in patients with IPF. While these observations are drawn from a single clinical trial, taken together with the preclinical data they suggest that nintedanib may yet become an important therapeutic option for individuals with IPF. The results of ongoing parallel, international, multicenter Phase III clinical trials are therefore eagerly awaited.

Keywords:

• interstitial lung disease
• BIBF 1120
• clinical trials
• usual interstitial pneumonia
• acute exacerbation

Disclosure

Toby M Maher is in receipt of an unrestricted academic industry grant from GlaxoSmithKline. In the last 3 years, TMM has received advisory board or consultancy fees from Actelion, Boehringer Ingelheim, GlaxoSmithKline, InterMune, Respironics, and Sanofi-Aventis. TMM has received speaker’s fees from UCB, Boehringer Ingelheim, and AstraZeneca. TMM’s institution has received an unrestricted educational grant from InterMune. Philip L Molyneaux’s institution has received reimbursement for his conference travel from Boehringer Ingelheim. Hannah V Woodcock has no conflicts of interest to declare.