Cystic fibrosis is caused by a reduced quantity or function of cystic fibrosis transmembrane conductance regulator (CFTR) protein, owing to mutations in CFTR. VX-661 is a first-generation CFTR corrector that has shown enhanced CFTR function and improved lung function in a phase 2 clinical trial involving patients who were homozygous for the Phe508del mutation or heterozygous for the Phe508del and G551D mutations [3]. The combination of VX-445 (2 μM) and VX-661 (18 μM) increased levels of mature CFTR protein and led to an increase in human bronchial epithelial cells from Phe508del–MF (a minimal-function mutation) and Phe508del–Phe508del (the Phe508del CFTR mutation) donors [4]. All doses of [VX-659-VX-661-ivacaftor] resulted in significant improvement in the percentage of predicted FEV1 (forced expiratory volume in 1 second) as compared with the respective within-group baseline values at day 29 in patients with Phe508del-MF or Phe508del-Phe508del genotypes [5].
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