The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) binds 
to the low-density lipoprotein (LDL) receptor (LDLR) and directs it to lysosomes 
for intracellular degradation. This results in decreased numbers of LDLR 
available on the hepatic cell surface to bind LDL particles and remove them from 
the circulation and therefore to a subsequent increase in circulating 
LDL-cholesterol (LDL-C) plasma levels. Since 2003, when the role of PCSK9 in 
LDL-C metabolism was discovered, there have been major efforts to develop 
efficient and safe methods to inhibit it. Amongst those, monoclonal antibodies 
against PCSK9 are the furthest in development, with multiple phase 3 trials 
already published and with cardiovascular endpoint trials currently underway. 
Two fully human monoclonal antibodies, evolocumab (AMG 145) and alirocumab 
(REGN727/SAR236553), have been extensively studied in a wide range of subjects, 
such as those with statin intolerance, as an add-on to statin therapy, as a 
monotherapy and in patients with familial hypercholesterolemia. PCSK9 antibodies 
result in a consistent and robust decrease in LDL-C plasma levels ranging from 
40% to 70%, either on top of statins or as a monotherapy. If the safety data 
from the on-going phase 3 trials remain as reassuring as the data available till 
now, PCSK9 antibodies will offer a novel, powerful therapeutic option to 
decrease LDL-C plasma levels and, hopefully, cardiovascular risk.