The triple fixed-dose combination (FDC), VX-659/tezacaftor/ivacaftor-FDC, is in clinical development for cystic fibrosis (CF) that is heterozygous for F508del mutation and a minimal function mutation for patients aged 12 years and older. CF is a life-limiting inherited disease that affects about 10,000 people in the UK. Genetic mutations affect the CF transmembrane conductance regulator (CFTR) gene, which is essential for the regulation of salt and water movements across cell membranes. These mutations mean that the CFTR protein is not processed and moved through the cells normally, resulting in little to no CFTR protein at the cell surface. This results in thickened secretions in organs with epithelial cell lining, mainly affecting the lungs and digestive system.
VX-659 and tezacaftor are designed to increase the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the F508del CFTR protein. Ivacaftor is designed to enhance the function of the CFTR protein once it reaches the cell surface. The triple therapy of VX-659/tezacaftor/ivacaftor-FDC may result in an effective therapeutic option for people with CF with F508del mutations, who currently have limited options.