Update on PCSK9 therapies for the treatment of dyslipidemia

The mechanistic role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in cholesterol metabolism has been well elucidated, and serves as an example of how genetics has informed modern drug development with the advent of PCSK9 inhibitors. PCSK9 is intimately involved in the hepatic regulation of the Low-density lipoprotein (LDL) receptor, which in turn plays a key role in the circulation of serum LDL. Monoclonal antibodies targeting PCSK9, which act by inhibiting PCSK9 thereby allowing for constitutively active LDL receptors, are now well established as an effective method for significant LDL lowering. Ongoing cardiovascular outcomes trials will hopefully highlight a concomitant and clinically meaningful reduction in adverse outcomes with their use. In the meantime, the PCSK9 journey, from initial discovery and description in 2003, to FDA approval in 2015, illustrates the interest and need for novel lipid therapies, as there are large populations for whom statin therapy alone is not adequate in optimizing their cardiovascular risk profile.