Evan A Stein1. 1. Metabolic and Atherosclerosis Research Center, Cincinnati, Ohio, USA.
Abstract
PURPOSE OF REVIEW: This article summarizes the role that the recently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) will play in LDL cholesterol management. RECENT FINDINGS: The discovery of PCSK9 in 2003 and its association with a rare form of autosomal-dominant hypercholesterolemia quickly led to the understanding of the role of circulating PCSK9 in regulating the recycling of the LDL receptor and LDL cholesterol (LDL-C) and impact on cardiovascular disease. Development of monoclonal antibodies that bind and inhibit PCSK9 entered clinical development in late 2009 and demonstrated substantial LDL-C reductions as monotherapy, added to statins, in heterozygous familial hypercholesterolemia and patients intolerant of statins. Large and comprehensive trials over the last 5 years also indicated good tolerability and safety and resulted in the 2015 regulatory approval in the USA and Europe for the marketing of two mAbs, evolocumab and alirocumab, for the treatment of LDL-C. SUMMARY: The background, clinical trials and approved indications for the current PCSK9 inhibitors are reviewed along with their likely role in the management of LDL-C and cardiovascular disease prevention.
PURPOSE OF REVIEW: This article summarizes the role that the recently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) will play in LDL cholesterol management. RECENT FINDINGS: The discovery of PCSK9 in 2003 and its association with a rare form of autosomal-dominant hypercholesterolemia quickly led to the understanding of the role of circulating PCSK9 in regulating the recycling of the LDL receptor and LDL cholesterol (LDL-C) and impact on cardiovascular disease. Development of monoclonal antibodies that bind and inhibit PCSK9 entered clinical development in late 2009 and demonstrated substantial LDL-C reductions as monotherapy, added to statins, in heterozygous familial hypercholesterolemia and patients intolerant of statins. Large and comprehensive trials over the last 5 years also indicated good tolerability and safety and resulted in the 2015 regulatory approval in the USA and Europe for the marketing of two mAbs, evolocumab and alirocumab, for the treatment of LDL-C. SUMMARY: The background, clinical trials and approved indications for the current PCSK9 inhibitors are reviewed along with their likely role in the management of LDL-C and cardiovascular disease prevention.
Authors: Ellen Q Wang; Jack F Bukowski; Carla Yunis; Charles L Shear; Paul M Ridker; Pamela F Schwartz; Daniel Baltrukonis Journal: BioDrugs Date: 2019-10 Impact factor: 5.807