WASHINGTON -- The novel drug ivacaftor (Kalydeco), formerly known as VX-770, has been approved for treating cystic fibrosis arising from the G551D-CFTR mutation, the FDA said Tuesday.
The drug is the first approved agent that targets abnormal chloride trafficking in cystic fibrosis, the condition's underlying cause.
"This is a breakthrough therapy for the cystic fibrosis community because current therapies only treat the symptoms of this genetic disease," said Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, in announcing the approval.
Found in 4% to 5% of cystic fibrosis patients, G551D-CFTR is the second most common genetic mutation after the delta F508-CFTR mutation, which is present in more than 90% of patients. An estimated 70,000 patients worldwide and 30,000 in the U.S. have cystic fibrosis.
Ivacaftor increases the time that activated CFTR channels at the cell surface remain open, allowing for more normal chloride flux in lung tissue.
The approval was based primarily on two phase III trials in which 213 patients received the drug or placebo.
In one involving adults, published last November in the New England Journal of Medicine, lung function as measured by forced expiratory volume in one second (FEV1) improved by 10.5 percentage points with ivacaftor relative to placebo after 48 weeks.
The drug was also associated with greater reductions in pulmonary exacerbations and respiratory symptoms, as well as better weight gain in the study. Patients with cystic fibrosis often have difficulty maintaining normal weight and are excessively thin.
The second trial was conducted in children and showed similar efficacy results, with an improvement in FEV1 of 10 percentage points.
Common side effects with ivacaftor include upper respiratory tract infection, headache, stomach ache, rash, diarrhea, and dizziness, the FDA said.
The drug should be taken twice daily with fat-containing foods, according to the agency.
Because ivacaftor is proven to be effective only in patients with the G551D mutation, patients' genotype should be determined before starting therapy, the FDA added. The drug had not been evaluated in children younger than 6.
The drug is produced by Vertex Pharmaceuticals. The company said it was evaluating a combination of ivacaftor and a different drug that Vertex believes could help patients with the more common delta F508-CFTR mutation.
Vertex said it would provide the drug free of charge to patients with household income of $150,000 or less who do not have insurance.
For those with insurance, the company said, "there will be a minimal out-of-pocket obligation after which Vertex will help cover copay or coinsurance costs up to 30% of the list price of the medicine. There is no income limit to be eligible for this program."