Pulmonary Fibrosis: Novel Tyrosine Kinase Inhibitor Promising

Despite considerable progress in the understanding of the mechanisms that drive pulmonary fibrosis, an effective treatment for this "relentlessly progressive and ultimately fatal disorder" has remained elusive, Dr. Gregory P. Downey wrote in an accompanying editorial.

However, recent studies have elucidated the role of a group of fibrogenic growth factors – including transforming growth factor (TGF)-beta, platelet-derived growth factor, connective-tissue growth factor, fibroblast growth factor, and vascular endothelial growth factor – in driving pulmonary fibrosis.

"Importantly, these growth factors produce signals through tyrosine kinase receptors or are linked to pathways controlled by tyrosine kinases," Dr. Downey wrote, noting that on the basis of this new understanding, selective tyrosine kinase inhibitors that target these fibrogenic pathways have been developed, including the potent intracellular tyrosine kinase inhibitor BIBF 1120 evaluated in this study by Dr. Richeldi and his colleagues.

BIBF 1120 inhibits a variety of growth factor receptors shown to regulate fibrogenic pathways. In animal models, inhibiting each of these receptor tyrosine kinases prevented development of pulmonary fibrosis, and indeed, in this human study, the effects of the agent are clinically relevant and represent an important advance, Dr. Downey said.

"As compared with other treatment approaches ... the beneficial effects of BIBF 1120 shine like a beacon over a turbulent sea of unfulfilled promises and failed clinical trials," he concluded, adding that newer inhibitors of fibrogenic pathways currently being developed promise to produce even more effective treatments.

Dr. Downey is with the division of pulmonary and critical care medicine at National Jewish Health in Denver, and the division of pulmonary sciences and critical care medicine at the University of Colorado at Denver. These comments were adapted from an editorial accompanying the report (N. Engl. J. Med. 2011;365:1140-1). Dr. Downey reported having no conflicts of interest.