Recovery of cystic fibrosis transmembrane conductance regulator (CFTR) functionality from nonclinical studies, and forced expiratory volume in 1 s (FEV1) and sweat chloride results from clinical trials for ivacaftor, lumacaftor and orkambi
Product | CFTR mutation in HBE cells in nonclinical studies | Recovery of CFTR functionality compared with wild-type % | CFTR mutation in patients for clinical trials | FEV1 % pred change | Sweat chloride change mmol·L−1 |
Ivacaftor | Homozygous F508del | <10 | Homozygous F508del | 1.7¶ | −2.9+ |
G551D/F508del | 48 | G551D/x mutation# | 10.5§ | −48.1ƒ | |
Lumacaftor | Homozygous F508del | 14 | Homozygous F508del | 0.47## | −8.2¶¶ |
Orkambi | Homozygous F508del | 25.1 | Homozygous F508del | 3.3++ | −9.5§§ |
HBE: human bronchial epithelial. #: patients that have the G551D mutation on at least one allele (the “x” stands for the G551D mutation or any other class I–V mutation [23]); ¶: absolute change in FEV1 % pred from baseline through week 16 between ivacaftor and placebo groups (the observed change was not statistically significant) [60]; +: sweat chloride reduction in the ivacaftor versus placebo groups from baseline through week 16 [60]; §: increase from baseline in FEV1 % pred through week 48 in the ivacaftor group compared with placebo [23]; ƒ: sweat chloride reduction in the ivacaftor versus placebo groups from baseline through week 48 [23]; ##: mean percentage change from baseline in FEV1 % pred at day 28 for a 200 mg dose [61]; ¶¶: mean treatment difference in sweat chloride from baseline (−placebo) at day 28 for a 200 mg dose [61]; ++: treatment difference obtained from the pooled data of two phase 3 pivotal studies for the average absolute change from baseline in FEV1 % pred at week 16 and 24 (dose: lumacaftor 600 mg/ivacaftor 250 mg) [58]; §§: treatment difference in sweat chloride from a phase 2 trial for the lumacaftor 600 mg once daily/ivacaftor 250 mg once every 12 h homozygous group compared with the pooled combination placebo group in the mean absolute change from baseline at day 56 [58].