Lumacafor/ivacaftor (fixed-dose combination) for cystic fibrosis homozygous for F508del mutation in patients aged 12 to 23 months

The fixed-dose combination (FDC) lumacaftor/ivacaftor-FDC is in clinical development for cystic fibrosis (CF) that is homozygous for F508del mutation for patients aged 12 to 23 months. CF is the most common, life-limiting recessively inherited (a faulty gene inherited from both parents) disease 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.
Lumacaftor is 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 combination therapy of lumacaftor/ivacaftor-FDC may result in an effective therapeutic option for young children with CF with F508del mutations, who currently have limited options.