Ofev (nintedanib) is an anti-fibrotic medicine marketed by Boehringer Ingelheim that was approved for the treatment of idiopathic pulmonary fibrosis (IPF) in the U.S. in 2014 and in Europe in 2015. The therapy also has been approved for the same indication in Japan and many other countries.
More recently, Ofev was approved in the U.S., Canada and Europe to treat patients with progressive fibrosing interstitial lung diseases (ILDs), a group of respiratory diseases characterized by progressive lung tissue scarring.
How does Ofev work?
Ofev inhibits tyrosine kinase, an enzyme essential for signal transduction pathways that trigger growth factors like vascular endothelial growth factor receptor, fibroblast growth factor receptor, and platelet-derived growth factor receptor, which are produced in excess in IPF patients.
These growth factors promote collagen production and deposition and control the differentiation, maturation, and proliferation of the fibroblasts, which eventually lead to the formation of scar tissue in the lungs.
By inhibiting tyrosine kinase and blocking these pro-fibrotic signaling mechanisms, Ofev is expected to slow the progression of IPF.
Ofev in clinical trials
The Phase 3 INPULSIS trials (NCT01335464 and NCT01335477) were the most decisive studies leading to Ofev’s original approval for the treatment of IPF in the U.S. and Europe. These trials involved a total of 1,066 patients from more than 24 countries.
Data from these studies demonstrated that Ofev was able to slow disease progression by reducing the rate of lung function decline, as measured by forced vital capacity (FVC), by 50% across a wide variety of patient subgroups. The therapy also reduced rates of adjudicated acute exacerbations by 68%. (Of note, FVC measures the total air a person is able to exhale after a deep breath.)
Additional analyses of these trials showed that Ofev was able to slow lung function decline regardless of disease severity. The therapy also was able to significantly lower the risk of acute flares reported as serious adverse side effects.
One-year data from a post-marketing survey that included 6,700 patients taking Ofev confirmed the treatment’s favorable safety and tolerability profile seen in prior studies.
A database study found no new safety concerns in four years of monitoring the clinical use of Ofev in people with IPF. The study showed the therapy’s safety and tolerability were consistent with results reported in previous trials.
Another important Ofev study was the Phase 2 TOMORROW trial (NCT00514683) and its open-label extension study (NCT01170065). Data from the main trial and its open-label extension study showed that Ofev was able to sustainably reduce lung function decline and disease progression over the course of more than a year.
Results from the Phase 3 INBUILD trial (NCT02999178) supported Ofev’s most recent approvals for the treatment of progressive fibrosing ILDs. The trial enrolled 663 adults with progressive fibrosing ILDs who were assigned randomly to receive 150 mg of Ofev or a placebo capsule, taken twice daily for one year.
Results showed that after one year, patients treated with Ofev had a slower FVC decline comparatively to those who were given a placebo (80.8 mL vs. 187.8 mL). These results suggested that Ofev was able to slow the rate of lung function decline by 57% compared with a placebo.
Results from INBUILD also demonstrated that symptoms, including coughing and shortness of breath, eased significantly in Ofev-treated patients. The trial also showed that treatment was similarly effective in all patients, regardless of their underlying ILD.
Other details
The most common side effects of Ofev are diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, decreased appetite, headache, weight loss, and high blood pressure.
According to Boehringer Ingelheim, the recommended dose for Ofev is one capsule of 150 mg twice daily (300 mg per day). It is advised that patients take the capsules with food during or immediately before or after a meal. For patients who do not tolerate the recommended dose of two 150 mg Ofev capsules per day, the daily dose may be reduced by their doctor.
Ofev is not recommended for patients with moderate or severe liver impairment. In patients with mild liver impairment (classified as Child-Pugh A), the recommended dose is 100 mg twice daily approximately 12 hours apart and taken with food. In these patients, liver enzymes (ALT, AST) and bilirubin should be monitored before and during treatment.
The safety and effectiveness of Ofev have not been studied in patients with severe kidney function impairment and end-stage kidney disease. Ofev may cause harm to the fetus and women should be advised about this potential risk. Breastfeeding while using Ofev is not recommended.
Last updated: May 20, 2021
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