TABLE 3.

Pharmacologic approaches to target PCSK9.

Class	Mechanism(s) of action	State of development
Monoclonal antibodies	Extracellular binding and neutralization of PCSK9	Positive outcome trials, evolocumab and alirocumab approved for clinical use
Small interfering RNA	Inhibition of intracellular PCSK9 production by PCSK9 mRNA degradation	Ongoing outcome trial with inclisiran, under approval
Antisense oligonucleotides		Terminated/preclinical
Vaccines	Induction of immune response against PCSK9	Phase 1
Adnectins	Binding of the LDL receptor-interacting PCSK9 region	Phase 1/2
Mimetic peptides	Competitive inhibitors mimicking the PCSK9-binding domain of the LDL receptor	Preclinical
Small molecules	Inhibition of PCSK9-LDL receptor interaction	Preclinical
	Inhibition of PCSK9 mRNA translation by blocking of the ribosome
	Blocking the binding of PCSK9 to the LDL-LDL receptor complex
	Blocking the interaction of PCSK9 and heparan sulfate proteoglycans which is necessary for the PCSK9-LDL receptor complex formation

Abbreviation: LDL, low-density lipoprotein. Data from Urban et al. (2013), Elbitar et al. (2016), Nishikido and Ray (2018), and Catapano et al. (2020).