Nintedanib inhibits fibroblast activation and ameliorates fibrosis in preclinical models of systemic sclerosis

Nintedanib inhibits macrophage activation and ameliorates vascular and fibrotic manifestations in the Fra2 mouse model of systemic sclerosis

“…Nintedanib may thus offer the potential to simultaneously inhibit multiple profibrotic pathways with a single drug. Indeed, we demonstrated potent antifibrotic effects of nintedanib in several preclinical models of skin fibrosis9 and a phase III clinical trial with nintedanib in SSc-associated interstitial lung disease is currently ongoing (SENSCIS trial; NCT02597933). However, the effects of nintedanib on vascular manifestations have not been investigated so far.…”

Translating Autoimmune Pathogenesis into Targeted Therapies for Systemic Sclerosis

“…Nintedanib is a tyrosine kinase inhibitor that targets the receptors of vascular endothelial growth factor, fibroblast growth factor and PDGF. It has been shown to retard the progression of idiopathic pulmonary fibrosis in phase III studies and reduce fibrosis in multiple mouse models of SSc [123,124]. Another candidate therapy worthy of mention is riociguat, a soluble guanylate cyclase stimulator that possesses both vasodilatory and anti-fibrotic properties.…”

From pathogenesis to therapy – Perspective on treatment strategies in fibrotic diseases

“…Nintedanib significantly reduced disease progression in two replicate phase 3 trials (INPULSIS-1 and INPULSIS-2) including more than 1000 patients with IPF and was approved by the Food and Drug Administration (FDA) for treatment of IPF in October 2014 (28). Huang et al showed anti-fibrotic effects of nintedanib in various in vivo models of SSc (25). These results together with the efficacy in IPF stimulated the initiation of a phase III clinical trial with nintedanib in SSc, which will start recruitment in the last quarter of 2015.…”

“…While imatinib rather selectively targets PDGFR and c-abl signaling, nintedanib (also known as BIBF 1120) blocks PDGFR alpha/beta, fibroblast growth factor receptor (FGFR)-1, 2, 3, VEGFR-1, 2, 3 and Src-family kinases Src, Lyn and Lck by blocking the intracellular ATP-binding pocket (25,26). Combined inhibition of different pro-fibrotic mediators is currently considered as a promising approach for the treatment of fibrosis (27).…”