General Information

Ofev (nintedanib) is a kinase inhibitor.

Ofev is specifically indicated for the following: 1) to slow the rate of decline in pulmonary function in patients with systemic sclerosis associated interstitial lung disease (SSc-ILD) and 2) to treat chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype

Ofev is supplied as a capsule for oral administration. The recommended dose for SSC-ILD is 150 mg twice daily administered approximately 12 hours apart.

Ofev capsules should be taken with food and swallowed whole with liquid. Ofev capsules should not be chewed or crushed because of a bitter taste. The effect of chewing or crushing of the capsule on the pharmacokinetics of nintedanib is not known. If a dose of Ofev is missed, the next dose should be taken at the next scheduled time. Advise the patient to not make up for a missed dose. Do not exceed the recommended maximum daily dosage of 300 mg.

Clinical Results

FDA Approval

The FDA approval of Ofev for systemic sclerosis-associated interstitial lung disease was based on SENSCIS, a Phase III double-blind, randomized, placebo-controlled trial, which enrolled 576 patients from 194 trial sites across 32 countries. The primary endpoint was the annual rate of decline in FVC in patients with SSc-ILD. Results shows that Ofev slowed the loss of pulmonary function by 44% (41 mL/year) in patients with SSc-ILD relative to placebo, as measured by FVC over 52 weeks. FVC is measured by the amount of air that can be forcibly exhaled after taking the deepest breath.

The FDA approval of Ofev for the treatment of chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype was based on INBUILD, a phase 3 randomized, double-blind, placebo-controlled trial in 663 adult patients with a mean age of 66 years. In the year-long trial, patients received 150 mg of Ofev twice a day or a placebo. The primary test for effectiveness was forced vital capacity. After the 52 weeks, Ofev slowed lung function decline by 57% compared to placebo, measured by the annual rate of decline in forced vital capacity (FVC).

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, colony stimulating factor 1 receptor (CSF1R), and Fms-like tyrosine kinase-3 (FLT-3). These kinases except for FLT-3 have been implicated in pathogenesis of interstitial lung diseases (ILD). Nintedanib binds competitively to the adenosine triphosphate (ATP) binding pocket of these kinases and blocks the intracellular signaling.
cascades, which have been demonstrated to be involved in the pathogenesis of fibrotic tissue remodeling in ILD. Nintedanib also inhibits the following nRTKs: Lck, Lyn and Src kinases. The contribution of FLT-3 and nRTK inhibition to nintedanib efficacy in ILD is unknown.