History of Ofev (nintedanib)
Ofev was approved by the U.S. Food and Drug Administration (FDA) in October 2014 and by the European Commission in January 2015 as a drug to treat IPF, following positive results from clinical trials (the INPULSIS Phase 3 study was the most decisive trial leading to the therapy’s approval).
In previous trials it was observed that the drug slowed disease progression by reducing the rate of decline in lung function (as measured by Forced Vital Capacity, or FVC) by 50 percent. The drug also reduced rates of adjudicated acute exacerbations by 68 percent. The INPULSIS trial involved 1,066 patients from more than 24 countries and was considered to be a major factor in the drug’s eventual approval.
How Ofev (nintedanib) works
Ofev inhibits tyrosine kinase, an enzyme essential for signal transduction pathways that trigger growth factors like vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet derived growth factor receptor (PDGFR), which are secreted in excess amounts in patients with IPF.
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.
Ofev binds to the phosphorylating site of tyrosine kinase, which blocks the cell signaling mechanism, slowing the progression of the disease.
Next steps for Ofev
Ofev has been approved by public health regulators and is considered to have an established safety and effectiveness profile. The next step for Boehringer Ingelheim is to determine the drug’s long-term effectiveness in managing IPF. At the 2015 International Conference of the American Thoracic Society (ATS), the company presented new data from the Phase 2 TOMORROW trial where patients were given the option to continue treatment with Ofev until they had completed the 52-week treatment period. The data shows the effect of the drug on slowing disease progression for up to 76 weeks. The results from this study were positive, showing that Ofev reduced the annual rate of FVC decline.
A new analysis of INPULSIS studies reinforced Ofev’s ability to slow disease progression in lung function decline and death. It has also shown a significant reduction in the risk of acute flares reported as serious adverse events. One-year data from post-marketing surveillance that included 6,700 patients taking Ofev confirmed the drug’s safety and tolerability profile seen in former studies.
Additional analyses of the INPULSIS study showed that Ofev slows the progression of pulmonary fibrosis regardless of the initial state of the participant, as measured by lung function.
Boehringer Ingelheim says 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 don’t tolerate the recommended dose of two 150 mg Ofev capsules per day, the daily dose may be reduced by their doctor.
The most common adverse side effects of the drug are diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, decreased appetite, headache, weight loss, and hypertension.
Ofev is not recommended for patients with moderate or severe liver impairment. In patients with mild liver impairment (Child Pugh A), the recommended dose is 100 mg twice daily approximately 12 hours apart 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 renal impairment and end-stage renal disease. Ofev may cause harm to the fetus and women should be advised about this potential risk. Breastfeeding while using Ofev is not recommended.
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