Vertex Pharmaceuticals has reported results from a phase II trial of VX-661 in combination with Kalydeco (ivacaftor) in patients with cystic fibrosis (CF) who have two copies of CFTR with the F508del mutation (ClinicalTrials.gov Identifier NCT02070744). The double-blind trial recruited 39 adult men and women and administered placebo (n = 18), 100 mg VX-661 once daily and 150 mg ivacaftor every 12 hours (n = 15), or 500 mg VX-661 every 12 hours and 150 mg ivacaftor every 12 hours (n = 6) for 12 weeks.
The drugs were well tolerated and there were no discontinuations due to adverse events. The most common adverse events were pulmonary exacerbation, which occurred in 38% of the VX-661 groups and 44% of the placebo group, and cough, which occurred in 33% of the VX-661 groups and 39% of the placebo group. Percent predicted FEV1 (ppFEV1) increased by 4.4 and 3.0 at 4 and 12 weeks, respectively, in the 100-mg VX-661 group, compared with changes of -0.4 and 1.0 at 4 and 12 weeks, respectively, for the placebo group and changes of 0.9 and 0.6 at 4 and 12 weeks, respectively, for the 50-mg VX-661 group.
Only the changes for the 100-mg VX-661 group were significant. This group also showed significant reductions in sweat chloride levels. Vertex has initiated phase III studies of 100 mg VX-661 once daily and 150 mg ivacaftor every 12 hours in an estimated 490 patients aged 12 years and older who are homozygous for the F508del mutation and another mutation resulting in a gating defect in CFTR in May 2015. Vertex also plans to start a phase III trial of the regimen in an estimated initial 120 patients aged 12 years and older who have one copy of the F508del mutation and have another mutation resulting in minimal CFTR function in mid-2015 (Vertex Pharmaceuticals News Release; ClinicalTrials.gov Web site).