General Information

Ofev (nintedanib) is a small molecule kinase inhibitor that blocks multiple pathways that may be involved in the scarring of lung tissue.

Ofev is specifically indicated for the treatment of idiopathic pulmonary fibrosis.

Ofev is supplied as a capsule for oral administration. The recommended dosage of Ofev is 150 mg twice daily administered approximately 12 hours apart. Ofev capsules should be taken with food and swallowed whole with liquid.

Clinical Results

FDA Approval

The FDA approval of Ofev was based on the results of one phase II and two phase III studies. These randomized, double-blind, placebo-controlled studies enrolled a total of 1,231 subjects and compared treatment with Ofev 150 mg twice daily to placebo for 52 weeks. The subjects were randomized to either Ofev 150 mg or placebo twice daily for 52 weeks. The phase II study also included other treatment arms (50 mg daily, 50 mg twice daily, and 100 mg twice daily). The primary endpoint was the annual rate of decline in Forced Vital Capacity (FVC). A statistically significant reduction in the annual rate of decline of FVC (in mL) was demonstrated in patients receiving OFEV compared to patients receiving placebo based on the random coefficient regression model, adjusted for gender, height, and age.

Mechanism of Action

Ofev (nintedanib) is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Nintedanib inhibits the following RTKs: platelet-derived growth factor receptor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR) 1-3, and Fms-like tyrosine kinase-3 (FLT3). Among them, FGFR, PDGFR, and VEGFR have been implicated in IPF pathogenesis. Nintedanib binds competitively to the adenosine triphosphate (ATP) binding pocket of these receptors and blocks the intracellular signaling which is crucial for the proliferation, migration, and transformation of fibroblasts representing essential mechanisms of the IPF pathology. In addition, nintedanib inhibits the following nRTKs: Lck, Lyn and Src kinases. The contribution of FLT3 and nRTK inhibition to IPF efficacy is unknown.