Results

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.

The triple fixed-dose combination (FDC), VX-445/tezacaftor/ivacaftor-FDC, is in clinical development for cystic fibrosis (CF) that is homozygous for F508del mutation for patients aged 12 years and older. 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.

The triple fixed-dose combination (FDC), VX-445/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 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.

Rivaroxaban is an already approved oral medicine used for the prevention of thrombotic vascular events in different types of artery diseases including PAD. It acts by blocking specific pathways involved in the process of blood clots within blood vessels, reducing the risk of a major vascular event. Aspirin alone is the current standard treatment in patients with PAD undergoing revascularization procedures but its risk reduction may not be adequate. If licensed rivaroxaban will potentially be an option as an add-on therapy in this patient group.

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.

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.

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 of tezacaftor and ivacaftor may result in an effective treatment for people with CF and may especially be a treatment option for those who cannot take a combination of ivacaftor and lumacaftor (another cystic fibrosis medicine), due to side effects or interactions with other medicines they are taking.