Dapagliflozin as a tablet is in clinical development for the treatment of heart failure (HF) with preserved ejection fraction. 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 (HFpEF), also referred to as diastolic heart failure, where the heart muscle contracts normally but the ventricles do not relax as they should during ventricular filling (or when the ventricles relax).
Dapagliflozin blocks the action of a protein in the kidneys called sodium-glucose co-transporter 2 (SGLT2). As blood is filtered by the kidneys, SGLT2 stops glucose in the bloodstream from being passed out into the urine. By blocking the action of SGLT2, dapagliflozin causes the kidney to pass out more glucose in the urine, thereby reducing the levels of glucose in the blood. Blood vessels can be damaged by the effects of high blood glucose levels and this can in turn cause damage to organs, such as the heart. Dapagliflozin may also increase the removal of fluid between tissue cells, contributing to reduced congestion with minimal impact on blood volume. If licensed, dapagliflozin may provide a treatment option for people with HFpEF who currently have no effective therapies available.
Gefapixant is an oral drug that blocks receptors in the sensory cells in the airways and lungs, potentially reducing cough frequency in patients with refractory or unexplained chronic cough. Preliminary results from early studies have demonstrated that gefapixant is efficacious and safe. If licenced, gefapixant could provide a treatment option for patients with refractory or unexplained cough who have no licensed therapies available and few effective therapies available.