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Vital capacity preserved in IPF with investigational agent nintedanib
Major finding: In the first trial, the adjusted annual rate of change in FVC was –114.7 mL with nintedanib versus –239.9 mL with placebo.
The Food and Drug Administration on Oct. 15 approved two new oral medications for idiopathic pulmonary fibrosis, Boehringer Ingelheim’s nintedanib (Ofev) and Roche’s pirfenidone (Esbriet).
The drugs significantly slowed the decline of forced vital capacity (FVC), compared with placebo, in phase III testing. They did not significantly reduce mortality. The FDA granted both agents fast track, priority review, orphan product, and breakthrough designations. Both were also approved ahead of schedule, according to the agency. Each of the drugs should be available for patients within the next 2 weeks, according to their manufacturers.
For pirfenidone, already on the market in Europe and Canada, Roche said it plans “a comprehensive patient support program designed to help with access, financial support, and ongoing education.”
For nintedanib, Boehringer Ingelheim plans “a comprehensive patient support program that will provide a broad range of financial and nursing support services,” called “Open Doors.” In testing, the most frequent serious adverse reactions with nintedanib, versus placebo, were bronchitis (1.2% versus 0.8%) and myocardial infarction (1.5% versus 0.4%). Pneumonia (0.7% versus 0.6%), lung cancer (0.3% versus 0%), and MI (0.3% versus 0.2%) were the most common fatal adverse events.
The most common side effects of nintedanib were diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, decreased appetite, headache, weight loss, and high blood pressure. Nintedanib is not recommended for patients who have moderate to severe liver problems or are pregnancy class D. Women of childbearing potential should use contraception for at least 3 months after stopping the drug, according to the FDA.
For pirfenidone, the most serious adverse events versus placebo were liver enzyme elevations (3.7% versus 0.8%), sensitivity to light or rash (9.0% versus 1.0%), and gastrointestinal side effects that caused 2.2 % of patients to discontinue treatment compared with 1.0% of those who received placebo.
The most common side effects of pirfenidone were nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, loss of appetite, gastroesophageal reflux, sinusitis, insomnia, decreased weight, and arthralgia.
The FDA warned about use of pirfenidone in patients with severe liver problems or end-stage kidney disease, or in those who require dialysis. Patients taking pirfenidone also must monitor and guard against sun exposure.
Clinical trials of pirfenidone included 1,247 idiopathic pulmonary fibrosis patients. In one with 555 patients, 17% of pirfenidone patients had an FVC decline of at least 10% after a year, compared with 32% who received placebo, Roche said.
Trials of nintedanib included 1,231 patients. One with 513 showed a relative reduction in annual FVC decline of 52% (–115 versus –240 mL for placebo) at 1 year, Boehringer Ingelheim noted.
