Anti-Human Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) (Evolocumab) (P720-GRP)

PCSK9 is a negative regulator of liver low-density lipoprotein (LDL)-receptors (LDLR)1 involved in maintaining lipoprotein homeostasis2. PCSK9 binds to LDLRs responsible for LDL-C removal from the bloodstream. PCSK9 binds to LDLRs at the surface of hepatocytes, preventing LDLR recycling, instead enhancing LDLR degradation3. This results in reduced numbers of LDLRs on liver cells and leads to high levels of circulating LDL-C2. Pathogenic variants of LDLR 2 or PCSK93 can be found in the autosomal dominant genetic disorder heterozygous familial hypercholesterolemia and can cause dysfunctional LDL-C metabolism and increased risk of premature atherosclerotic cardiovascular disease. Some patients with hypercholesterolemia, regardless of cause, are not able to attain target LDL-C levels with statins or ezetimibe, in which case monoclonal antibodies that inhibit PCSK9 can be used as an additional management tool2. AMG-145 (Evolocumab) is a PCSK9 inhibitor that limits the levels of circulating LDL-C4,5. Evolocumab prevents PCSK9-mediated degradation of LDLRs, and thereby increases LDLR availability on the liver surface. This results in increased removal of LDL-C from serum. Evolocumab was humanized from a mouse monoclonal antibody6. Evolocumab was developed for the treatment of hyperlipidemia, including hypercholesterolemia4.