The US FDA has approved Boehringer Ingelheim’s Ofev (nintedanib) oral capsules to treat patients with chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype. It is the first FDA-approved treatment for this group of fibrosing lung diseases that worsen over time, according to the agency.
Ofev was previously approved to treat idiopathic pulmonary fibrosis and to slow the rate of decline in pulmonary function among patients with ILD associated with systemic sclerosis or scleroderma.
According to Boehringer Ingelheim, unclassifiable ILDs, autoimmune ILDs, chronic hypersensitivity pneumonitis, sarcoidosis, myositis, sjogren’s syndrome, coal workers pneumoconiosis and idiopathic forms of interstitial pneumonias such as idiopathic non-specific interstitial pneumonia are among the diseases that may develop a progressive form of chronic fibrosing ILD.
The FDA approval is based on the INBUILD trial, the first Phase III clinical trial in the field of ILDs to group patients based on the clinical behavior of their disease rather than the primary clinical diagnosis. In this trial, the safety and tolerability profile of Ofev was consistent with what was previously seen in IPF studies. The most common adverse reactions reported in greater than or equal to five percent in Ofev-treated patients compared to placebo were diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, decreased appetite, weight decreased, headache, hypertension, nasopharygitis, upper respiratory tract infection, urinary tract infections, fatigue and back pain. Please see additional Important Safety Information included below.
“The FDA continues to encourage the development of therapies for patients with limited or no treatment options,” said Banu Karimi-Shah, MD, acting deputy director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval helps to fulfill an unmet treatment need, as patients with these life-threatening lung diseases have not had an approved medication until now.”
Ofev’s safety and effectiveness to treat chronic fibrosing ILD with a progressive phenotype in adults was evaluated in a randomized, double-blind, placebo-controlled study of 663 adults. The mean age of patients was 66 years and more patients were male (54%) than female. The primary test for effectiveness was the forced vital capacity, which is a measure of lung function. It is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. In the 52-week period, patients received either 150 milligrams of Ofev twice a day or a placebo. After 52 weeks, people who received Ofev had less lung function decline compared to those on the placebo.
The most common side effects reported in the Ofev clinical trial were diarrhea, nausea, stomach pain, vomiting, liver problems, decreased appetite, headache and weight loss. Ofev is not recommended for patients with moderate or severe hepatic (liver) impairment. Elevated liver enzymes and drug-induced liver injury and gastrointestinal disorders have occurred among people taking Ofev. It may also cause embryo-fetal toxicity that can result in fetal harm, arterial thromboembolic events (blood clots), bleeding and gastrointestinal perforation (hole formation). P-glycoprotein and CYP3A4 inhibitor drugs, including ketoconazole and erythromycin, may increase nintedanib exposure, and patients taking these inhibitors with Ofev should be closely monitored.
Ofev received Priority Review designation, meaning the agency plans to take action on the application within six months because the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition. It also received Breakthrough Therapy Designation, which is designed to expedite the development and review of certain drugs intended to treat a serious condition.