The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
cystic fibrosis with the G551D mutation in the CFTR gene
Kalydeco (ivacaftor) is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator. Cystic fibrosis is caused by mutations in a gene that encodes for the CFTR protein that regulates ion (such as chloride) and water transport in the body. The defect in chloride and water transport results in the formation of thick mucus that builds up in the lungs, digestive tract and other parts of the body leading to severe respiratory and digestive problems.
Kalydeco was specifically approved for the treatment of cystic fibrosis in patients age 6 years and older who have a G551D mutation in the CFTR gene. If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the G551D mutation.
Kalydeco is supplied as a tablet for oral administration. The recommended dose of Kalydeco for both adults and pediatric patients age 6 years and older is one 150 mg tablet taken orally every 12 hours (300 mg total daily dose).
The FDA approval of Kalydeco was based on the following trials:
A double-blind, placebo-controlled, cross-over trial enrolled 39 adult subjects. Twenty subjects with median predicted FEV1 at baseline of 56% received Kalydeco 25, 75, 150 mg or placebo every 12 hours for 14 days and 19 subjects with median predicted FEV1 at baseline of 69% received Kalydeco 150, 250 mg or placebo every 12 hours for 28 days. The optimal dose was determined to be 150 mg every 12 hours.
Two randomized, double-blind, placebo-
controlled clinical trials enrolled 213 clinically stable subjects who received Kalydeco 150 mg twice daily or placebo every 12 hours with food containing fat for 48 weeks in
addition to their prescribed CF therapies. Trial 1 enrolled 161 subjects who were 12 years of age or older with baseline FEV1 between 40-90% predicted. Trial 2 evaluated 52 subjects who were 6 to 11 years of age with baseline FEV1 between 40-105% predicted. The primary efficacy endpoint in both studies was improvement in lung function as determined by the mean absolute change from baseline in percent predicted pre-dose FEV1 through 24 weeks of treatment. In both studies, treatment with Kalydeco resulted in a significant improvement in FEV1. The treatment difference between Kalydeco and placebo for the mean absolute change in percent predicted FEV1 from baseline through Week 24 was 10.6 percentage points (P < 0.0001) in Trial 1 and 12.5 percentage points (P < 0.0001) in Trial 2. These changes persisted through 48 weeks.
Adverse events associated with the use of Kalydeco may include, but are not limited to, the following:
- oropharyngeal pain
- upper respiratory tract infection
- nasal congestion
- abdominal pain
Mechanism of Action
Kalydeco (ivacaftor) is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator. The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs. Ivacaftor facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the G551D-CFTR protein. Cystic fibrosis is caused by mutations in a gene that encodes for the CFTR protein that regulates ion (such as chloride) and water transport in the body. The defect in chloride and water transport results in the formation of thick mucus that builds up in the lungs, digestive tract and other parts of the body leading to severe respiratory and digestive problems.
Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Drevínek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordoñez C, Elborn JS; VX08-770-102 Study Group A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. The New England Journal of Medicine 2011 Nov 3;365(18):1663-72.
Accurso FJ, Rowe SM, Clancy JP, Boyle MP, Dunitz JM, Durie PR, Sagel SD, Hornick DB, Konstan MW, Donaldson SH, Moss RB, Pilewski JM, Rubenstein RC, Uluer AZ, Aitken ML, Freedman SD, Rose LM, Mayer-Hamblett N, Dong Q, Zha J, Stone AJ, Olson ER, Ordoñez CL, Campbell PW, Ashlock MA, Ramsey BW Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. The New England Journal of Medicine 2010 Nov 18;363(21):1991-2003
For additional information regarding Kalydeco or cystic fibrosis, please visit the Kalydeco web page.