Combination lumacaftor and ivacaftor therapy for cystic fibrosis

Abstract

ABSTRACTIntroduction: Cystic fibrosis (CF) is a life-shortening autosomal recessive genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, causing pancreatic insufficiency, progressive bronchiectasis that leads to respiratory failure, and other organ system disease. Ivacaftor, the first commercially available therapy that improves CFTR function, has been available for patients with “gating” CFTR mutations since 2012. Lumacaftor combined with ivacaftor was recently demonstrated to improve lung function and reduce pulmonary exacerbation frequency in CF patients who are homozygous for the F508del mutation, the most prevalent CFTR mutation worldwide.Areas covered: This article discusses basic discoveries leading to the development of lumacaftor-ivacaftor combination therapy, and results of phase 2 and 3 clinical trials. Articles were accessed via PubMed using the search terms VX-809 and lumacaftor; supplemental information was accessed using Google Search and the United States National Institutes of Health clinical trials website.Expert opinion: Combination lumacaftor and ivacaftor therapy confers benefit in the treatment of F508del homozygous cystic fibrosis, most notably in reduction of pulmonary exacerbation. The pulmonary function and nutritional benefits are modest compared to ivacaftor monotherapy in CF patients with gating mutations, and efforts are underway to optimize CFTR correction.