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

被引:34
作者
Woodcock, Hannah V. [1 ,2 ]
Molyneaux, Philip L. [1 ,3 ]
Maher, Toby M. [1 ,2 ,3 ]
机构
[1] Royal Brompton Hosp, Interstitial Lung Dis Unit, London SW3 6NP, England
[2] UCL, Ctr Resp Res, London, England
[3] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England
来源
DRUG DESIGN DEVELOPMENT AND THERAPY | 2013年 / 7卷
关键词
interstitial lung disease; BIBF; 1120; clinical trials; usual interstitial pneumonia; acute exacerbation; TRIPLE ANGIOKINASE INHIBITOR; FIBROBLAST-GROWTH-FACTOR; PLACEBO-CONTROLLED TRIAL; LABEL DOSE-ESCALATION; TYROSINE KINASE INHIBITOR; ADVANCED SOLID TUMORS; I OPEN-LABEL; BIBF; 1120; PHASE-I; TGF-BETA;
D O I
10.2147/DDDT.S38833
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
引用
收藏
页码:503 / 510
页数:8
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