An update on the clinical development of proprotein convertase subtilisin kexin 9 inhibitors, novel therapeutic agents for lowering low-density lipoprotein cholesterol.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an essential role in the degradation of low-density lipoprotein C (LDL-C) receptors, and PCSK9 inhibitors have recently emerged as a potential treatment option to reduce LDL-C. Our paper reviewed the current available Phase II clinical trials of PCSK9 inhibitors for the treatment of dyslipidemia. A second objective of this review was to evaluate the potential clinical role of PCSK9 inhibitors in the management of dyslipidemia. Studies evaluating the efficacy and safety of any PCSK9 inhibitors in patients with dyslipidemia were included. The monoclonal antibodies REGN727/SAR236553 and AMG145 have the most published clinical data. Seven phase II trials were retrieved that evaluated the efficacy and safety of REGN727/SAR236553 or AMG145 in patients with either hypercholesterolemia or heterozygous familial hypercholesterolemia (HeFH). These two agents significantly decreased LDL-C levels either as monotherapy or in combination with other lipid-lowering agents. REGN727/SAR236553 and AMG145 have been well tolerated. The ongoing phase III trials of these two agents are summarized. REGN727/SAR236553 and AMG145 have demonstrated the potential to further decrease LDL-C levels when added to conventional lipid-lowering therapy. Morbidity and mortality data are required to define their roles in clinical practice.