Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508delCFTR

Abstract

Cystic fibrosis is a life-limiting disease that is caused by defective or deficient cystic fibrosis transmembrane conductance regulator (CFTR) protein activity. Phe508del is the most common CFTR mutation. We conducted two phase 3, randomized, double-blind, placebo-controlled studies that were designed to assess the effects of lumacaftor (VX-809), a CFTR corrector, in combination with ivacaftor (VX-770), a CFTR potentiator, in patients 12 years of age or older who had cystic fibrosis and were homozygous for the Phe508del CFTR mutation. In both studies, patients were randomly assigned to receive either lumacaftor (600 mg once daily or 400 mg every 12 hours) in combination with ivacaftor (250 mg every 12 hours) or matched placebo for 24 weeks. The primary end point was the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV₁) at week 24. A total of 1108 patients underwent randomization and received study drug. The mean baseline FEV₁ was 61% of the predicted value. In both studies, there were significant improvements in the primary end point in both lumacaftor–ivacaftor dose groups; the difference between active treatment and placebo with respect to the mean absolute improvement in the percentage of predicted FEV₁ ranged from 2.6 to 4.0 percentage points (PCFTR mutation. (Funded by Vertex Pharmaceuticals and others; TRAFFIC and TRANSPORT ClinicalTrials.gov numbers, NCT01807923 and NCT01807949.)