WASHINGTON -- The FDA has approved the phosphodiesterase-4 inhibitor roflumilast (Daliresp) to prevent COPD exacerbations, despite a negative advisory panel vote last year.
Last April, the FDA's Pulmonary-Allergy Drugs Advisory Committee voted 10-5 that the drug's "modest" benefits failed to outweigh its side effects.
Among patients taking roflumilast in clinical trials, 14% discontinued the drug because of problems that included weight loss, psychiatric events including suicide, and the potential for cancer. Diarrhea and nausea were the leading causes of discontinuation.
Also of concern to the advisory panel were three suicides and two suicide attempts in roflumilast patients, compared with no suicides or suicide attempts in patients receiving placebo, and a greater incidence of cancer in patients taking the drug.
On the plus side, once-daily treatment with 500 mcg of roflumilast reduced the rate of moderate or severe exacerbations by 15% in one 12-month trial and by 18% in another.
The drug also improved one-second forced expiratory volume (FEV1) by 48 mL, which FDA staff had described to the advisory panel as "modest."
But in announcing the approval, the director of the FDA's Office of Drug Evaluation II suggested the benefits were significant.
"New treatment options that reduce frequency of flare-ups or exacerbations are important in helping patients with COPD associated with chronic bronchitis and a history of exacerbations in managing this debilitating disease," said Curtis Rosebraugh, MD, MPH, in a statement.
As part of the approval, the FDA is requiring that the drug's U.S. manufacturer, Forest Laboratories, distribute a medication guide for patients that describes the risks of mental health problems and weight loss.
Roflumilast should not be used to treat sudden breathing problems (acute bronchospasm), and is not recommended for people younger than 18, the FDA said.
The most common side effects reported by patients in the clinical trials included diarrhea, nausea, headache, insomnia, back pain, decreased appetite, and dizziness.
More than 4,400 patients received the drug in the clinical trials, according to Forest.