TABLE 4

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

ProductCFTR mutation in HBE cells in nonclinical studiesRecovery of CFTR functionality compared with wild-type %CFTR mutation in patients for clinical trialsFEV1 % pred changeSweat chloride change mmol·L−1
IvacaftorHomozygous F508del<10Homozygous F508del1.7−2.9+
G551D/F508del48G551D/x mutation#10.5§−48.1ƒ
LumacaftorHomozygous F508del14Homozygous F508del0.47##−8.2¶¶
OrkambiHomozygous F508del25.1Homozygous F508del3.3++−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].