Firibastat Brain aminopeptidase A inhibitor, Treatment of difficult-to-treat or resistant hypertension, Treatment of heart failure

摘要

An estimated 1.13 billion people worldwide have hypertension, and its related complications account for 10.4 million deaths worldwide every year. The brain aminopeptidase A (APA) generates angiotensin III (Ang III), which plays a central role in brain renin-angiotensin system (RAS) hyperactivity and hypertension, making APA an attractive target for hypertension treatment. Firibastat (R8150, QGC001) is a first-in-class brain APA inhibitor. In relevant models of hypertension in rats, firibastat given orally inhibited brain APA activity, blocked the formation of brain Ang Ill and decreased blood pressure (BP); and in rodent models of myocardial infarction (M1) it prevented cardiac dysfunction. In a phase II study in hypertensive overweight patients, including Black individuals, oral firibastat showed safety and efficacy lowering BP Phase III studies are now underway to assess firibastat in difficult-to-treat or resistant hypertension. A phase II study is also ongoing to compare firibastat with ramipril to prevent left ventricular dysfunction after acute MI.