Ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation

Abstract

Cystic fibrosis (CF) is an autosomal recessive lethal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes for CFTR, an epithelial cell-surface expressed protein responsible for the transport of chloride (Cl^-). Gating mutations associated with defective conductance can be modulated by CFTR potentiators. Ivacaftor is a CFTR potentiator approved for the treatment of CF patients >6 yrs of age with at least one copy of the G551D-CFTR mutation. Herein, the clinical trial development programme for ivacaftor will be reviewed, including two pivotal studies in adolescents/adults and in children. These studies report sustained improvements in lung function and sweat chloride concentrations, and a reduction in pulmonary exacerbations over a 48-week treatment period. In the era of personalised medicine, ivacaftor offers an effective and well-tolerated treatment for the clinical management of CF patients with the G551D mutation. A long-term, open-label study will report the effects of ivacaftor over a further 48 weeks.