Tezacaftor/ivacaftor (fixed-dose combination) for cystic fibrosis heterozygous for F508del mutation and one residual mutation in patients aged 6 to 11 years

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Indications: Cystic fibrosis
Therapeutic Areas: Genetic Disorders , Respiratory System
Year: 2019

The fixed-dose combination (FDC) tezacaftor/ivacaftor-FDC is in clinical development for cystic fibrosis (CF) that is heterozygous for F508del mutation and a residual mutation for patients aged 6 to 11 years. 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.
Tezacaftor 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 tezacaftor/ivacaftor-FDC (Symkevi) has been approved in the EU for patients aged 12 years and older with CF that have one of these gene mutations. If approved, this licence extension would mean that patients with these gene mutations could have access to this treatment regimen at an earlier age.