Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 37 S2.3 | DOI: 10.1530/endoabs.37.S2.3

ECE2015 Symposia Management of type 2 diabetes: State of the art (3 abstracts)

PCSK9 antibodies for the treatment of hypercholesterolemia

Ioanna Gouni-Berthold

University of Cologne, Cologne, Germany.

Cardiovascular disease (CVD) is the leading cause of death worldwide accounting for more than 17 million deaths just in 2012. A major culprit for the development of CVD is an elevated low density lipoprotein (LDL) cholesterol (LDL-C) concentration. Despite statin therapy a high residual risk of cardiovascular events remains, especially since with the currently available treatment options only ~50% of high risk patients and ~20% of very high risk patients achieve their target LDL-C values of <100 and <70 mg/dl respectively. It is therefore clear that additional therapies are needed. The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to LDL receptor (LDLR) and directs it to lysosomes for intracellular degradation. This results in, decreased numbers of LDLR available on the hepatic cell surface to bind LDL particles and remove them from the circulation and therefore to a subsequent increase in circulating LDL-C concentrations. Since 2003, when the role of PCSK9 in LDL-C metabolism was discovered, there have been major efforts to develop efficient and safe methods to inhibit it. Amongst those, monoclonal antibodies against PCSK9 are the furthest in development, with multiple phase 3 trials already published and with cardiovascular endpoint trials currently underway. Two fully human monoclonal antibodies, evolocumab and alirocumab, have been extensively studied in a wide range of subjects, such as those with statin intolerance, as an add-on to statin therapy, as a monotherapy and in patients with familial hypercholesterolemia. PCSK9 antibodies result in a consistent and robust decrease in LDL-C plasma levels ranging from 40% to 70%, either on top of statins or as monotherapy. If the safety data from the on-going phase 3 trials remain as reassuring as the data available till now, PCSK9 antibodies will offer a novel, powerful therapeutic option to decrease LDL-C plasma levels and, hopefully, cardiovascular risk.

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