Evolocumab for the treatment of hypercholesterolemia.

Evolocumab is a fully human monoclonal immunoglobulin G2 directed against human proprotein convertase subtilisin/kexin type 9 (PCSK9). It is administered by subcutaneous injection every 2 weeks or once monthly. Area covered: Herein, the authors discuss the rationale for inhibiting PCSK9 and describe the pharmacodynamics, pharmacokinetics and clinical trials with evolocumab. Evolocumab reduces low density lipoprotein cholesterol (LDL-C) levels by 50 to 60% in most patients with and without background treatment with statins or other lipid lowering agents. The safety profile appears satisfactory from the completed clinical studies and concerns regarding the risk of neurocognitive events have largely been dispelled. Expert opinion: The reduction of LDL-C with evolocumab to previously unattainable levels has resulted in a reduction in the composite cardiovascular event endpoint in the FOURIER trial and this is likely to impact on future lipid management guidelines. The clinical outcome data and excellent tolerability profile clearly support the use of evolocumab in patients at high cardiovascular risk, including those with heterozygous or homozygous familial hypercholesterolemia, who are unable to achieve LDL-C targets with statins with or without other lipid-lowering drugs. The high cost of evolocumab will restrict its use, however.