Ivacaftor improves lung function in cystic fibrosis

A randomized trial of ivacaftor, a potentiator of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein, in patients with CF demonstrated that its use is not only associated with improvements in lung function but also with improvements in the risk of pulmonary exacerbations, respiratory symptoms, weight, and concentration of sweat chloride.

Seventy-seven patients aged 12 years and older (mean age, 25.5 years) taking ivacaftor and 68 taking placebo completed 48 weeks of treatment; all had at least 1 allele of the G551D-CFTR mutation, the most prevalent of the CF mutations that adversely affect the function of CFTR channels at cell surfaces.

Patients received either ivacaftor 150 mg every 12 hours or placebo throughout the study period along with their prestudy medications. Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through the entire 48 weeks of treatment. At 24 weeks, the number of patients taking ivacaftor had increased 10.4 percentage points from baseline in the percent of predicted forced expiratory volume in 1 second (FEV₁) compared with a decrease of 0.2 percentage points in the placebo group. At week 48, the percent of predicted FEV₁ in the ivacaftor group was 10.5 percentage points greater than in the placebo group.

COMMENTARY

For the 4% or 5% of patients with CF with this mutation on at least 1 of their CFTR genes, this work may offer immediate and substantial improvement in many measures of their disease. The broader importance of this medication is that it represents an allele-specific therapy, among the first of what may become common, directed therapies for CF and many other genetic diseases.-Michael Burke, MD