Combination Therapy in Patients with Cystic Fibrosis Targets Underlying Dysfunction

Mutations in the gene for cystic fibrosis transmembrane conductance regulator (CFTR) protein, an anion channel in the epithelial cell membrane, result in abnormal amounts or activity of the protein. About 45% of patients with cystic fibrosis are homozygous for the most common CFTR mutation (Phe508del); median survival among this cohort in the U.S. is 37 years.

Researchers studied a combination of a recently approved drug, ivacaftor, and an investigational drug, lumacaftor, in two phase III, randomized, double-blind, placebo-controlled, industry-sponsored trials. Lumacaftor, a CFTR corrector, increases the amount of protein on the epithelial cell surface in vitro. Ivacaftor, a CFTR potentiator, increases the percentage of time the anion chann…