Ofev (nintedanib) - 3 indications

Scroll down for information on each indication:

• the treatment of idiopathic pulmonary fibrosis; approved October 2014
• the treatment of systemic sclerosis-associated interstitial lung disease; approved September 2019
• the treatment of chronic fibrosing interstitial lung diseases with a progressive phenotype; approved March of 2020

General Information

Ofev (nintedanib) is a kinase inhibitor.

Ofev is specifically indicated for the following:

• for the treatment of idiopathic pulmonary fibrosis
• to slow the rate of decline in pulmonary function in patients with systemic sclerosis associated interstitial lung disease (SSc-ILD)
• for the treatment of chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype

Ofev is supplied as a capsule for oral administration. The recommended dose for all indications 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.

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. 

Side Effects

Adverse effects associated with the use of Ofev may include, but are not limited to, the following:

• diarrhea
• nausea
• abdominal pain
• vomiting
• liver enzyme elevation
• decreased appetite
• headache
• weight decreased
• hypertension

Indication 1 - idiopathic pulmonary fibrosis

approved October 2014

Clinical Trial Results

The FDA approval of Ofev for idiopathic pulmonary fibrosis 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.

Indication 2 - the treatment of systemic sclerosis-associated interstitial lung disease

approved September 2019

Clinical Trial Results

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.

Indication 3 - chronic fibrosing interstitial lung diseases with a progressive phenotype

approved March of 2020

Clinical Trial Results

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).