In 2012, the Food and Drug Administration approved the oral drug ivacaftor for treatment in patients over six years of age with a specific mutation of CFTR: G511D. This was the first drug to target the gene defect and not the symptoms of CF. G551D is a class III mutation and accounts for about 4% of CF cases. In this mutation, CFTR is synthesized and moves to the cell membrane, but the chloride channel does not function. In clinical trials, patients on ivacaftor had improvement in lung function, decreased sweat chloride concentrations, and increased weight gain compared to placebo.
ORKAMBI® is a combination of ivacaftor and a second drug, lumacaftor. It is indicated for the treatment of CF in patients aged six years and older who have two copies of the most common CFTR mutation, F508del. (If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene). The efficacy and safety of ORKAMBI® has not been established in patients with CF other than those homozygous for the F508del mutation.
Studies are ongoing to test the safety and efficacy of these newer drugs in younger patients, as well as novel drugs to treat other mutations of CFTR.
