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.

• Authors: Hannah V Woodcock, Philip L Molyneaux, Toby M Maher
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 7 Pg. 503-10 ( 2013) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 23818761 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Indoles
• Protein Kinase Inhibitors
• ErbB Receptors
• Receptors, Platelet-Derived Growth Factor
• Receptors, Vascular Endothelial Growth Factor
• nintedanib

Topics

• Clinical Trials, Phase II as Topic
• ErbB Receptors (antagonists & inhibitors)
• Humans
• Idiopathic Pulmonary Fibrosis (drug therapy, physiopathology)
• Indoles (adverse effects, pharmacokinetics, therapeutic use)
• Lung (physiopathology)
• Protein Kinase Inhibitors (therapeutic use)
• Receptors, Platelet-Derived Growth Factor (antagonists & inhibitors)
• Receptors, Vascular Endothelial Growth Factor (antagonists & inhibitors)