Ivacaftor (trade name Kalydeco, developed as VX-770) is a drug used to treat cystic fibrosis in people with certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, who account for 4–5% cases of cystic fibrosis, and is included in a combination drug, lumacaftor/ivacaftor, which is used to treat people with cystic fibrosis who have the F508del mutation in CFTR.
Ivacaftor was developed by Vertex Pharmaceuticals in conjunction with the Cystic Fibrosis Foundation and is the first drug that treats the underlying cause rather than the symptoms of the disease. It was approved by the FDA in January 2012, and was called "the most important new drug of 2012", and "a wonder drug". It is one of the most expensive drugs, costing over US$300,000 per year, which has led to criticism of Vertex for the high cost. The combination drug was approved by the FDA in July 2015.
Cystic fibrosis is caused by any one of several defects in the CFTR protein, which regulates fluid flow within cells and affects the components of sweat, digestive fluids, and mucus. One such defect is the G551D mutation, in which the amino acid glycine(G) in position 551 is replaced with aspartic acid(D). G551D is characterized by a dysfunctional CFTR protein on the cell surface. In the case of G551D, the protein is trafficked to the correct area, the epithelial cell surface, but once there the protein cannot transport chloride through the channel. Ivacaftor, a CFTR potentiator, improves the transport of chloride through the ion channel by binding to the channels directly to induce a non-conventional mode of gating which in turn increases the probability that the channel is open.