Anti-PCSK9 therapies for the treatment of hypercholesterolemia.

INTRODUCTION: Proprotein convertase subtilisin kexin type 9 (PCSK9), a serine protease that binds to the low density lipoprotein (LDL) receptor promoting its degradation, is an important regulator of LDL metabolism. PCSK9 'gain-of-function' mutations are rare and cause high plasma LDL-cholesterol and increase atherosclerotic cardiovascular disease, whereas more common 'loss-of-function' mutations cause low LDL-cholesterol and atheroprotection. PCSK9 is a novel, attractive and viable therapeutic target for the treatment of hypercholesterolemia, with human studies using a variety of anti-PCSK9 therapies underway. AREAS COVERED: This review summarizes the latest findings in clinical trials of PCSK9 inhibitors, including antibodies, gene silencing and small peptides. EXPERT OPINION: PCSK9 inhibition would appear to be an effective strategy for lowering plasma LDL-cholesterol and enhancing the LDL-cholesterol lowering ability of statins in patients with familial hypercholesterolemia, patients with refractory hypercholesterolemia at high risk of cardiovascular disease and patients with severe hypercholesterolemia who are not at target or are intolerant of statins, with a variety of anti-PCSK9 therapies in clinical trials.