Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density 
lipoprotein receptor, escorting it to its destruction in the lysosome and 
thereby preventing the recirculation of the low-density lipoprotein receptor to 
the hepatocyte cell surface. Both gain-of-function mutations in PCSK9 (causing 
marked increases in low-density lipoprotein cholesterol [LDL-C] concentration 
and premature atherosclerosis) and loss-of-function mutations (causing modest 
LDL-C reduction with low rates of coronary heart disease) have been described. 
Several monoclonal antibodies to PCSK9 have achieved LDL-C reductions of 50% to 
70% across various patient populations and background lipid therapies. Phase 2/3 
trials have demonstrated good tolerability without clear drug-related toxicity, 
although the number and duration of patients treated to date is modest. 
Currently, 4 phase 3 trials involving >70,000 patients are testing whether these 
drugs reduce cardiovascular events. The U.S. Food and Drug Administration is 
currently reviewing the existing data to determine whether these agents could be 
made available prior to the completion of these cardiovascular endpoint trials 
expected in 2018.