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.
Angiotensin II acetate is in clinical development for the treatment of catecholamine and/or vasopressin resistant hypotension due to distributive shock. Shock is a critical condition in which blood pressure drops so low that the brain, kidneys and other vital organs cannot receive enough blood flow to function properly. Distributive shock is the most common type of shock that is most commonly caused by bacterial or fungal infection (septic shock) or allergic reaction (anaphylactic shock). Severe shock is usually treated with drugs called catecholamines or vasopressin. Shock that does not respond to treatment with these drugs is resistant shock.