Entresto (a tablet comprising a combination of the drugs sacubitril and valsartan), is in clinical development for people with chronic heart failure with preserved ejection fraction. Heart Failure (HF) is a complex clinical syndrome of symptoms and signs that suggest the efficiency of the heart as a pump is impaired. Symptoms include breathlessness and fatigue, and signs of the condition include swollen ankles and crackling sounds in the lungs. People with HF often have a poor quality of life, and about a third of people experience severe and prolonged depressive illness. About half of people with HF have a preserved ejection fraction (HF-PEF), meaning that over 50% of the blood in the left ventricle is pumped out with each contraction of the heart.
Entresto is licensed in the UK for treating people with HF with a reduced ejection fraction. The drug combination works by augmenting the actions of natriuretic peptides, which defend the heart from volume and pressure overload. Trials have shown that treatment with Entresto can reduce pressure and wall stress in the left ventricle. If licensed, Entresto could provide a treatment for people with HF-PEF, who currently have no effective treatments available.
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.