Efficacy and safety profile of evolocumab (AMG145), an injectable inhibitor of the proprotein convertase subtilisin/kexin type 9: the available clinical evidence

Abstract

Introduction: Despite the proven efficacy of statins, they are often reported to be inadequate to achieve low-density lipoprotein cholesterol (LDL-C) goals (especially in high-risk patients). Moreover, a large number of subjects cannot tolerate statins or full doses of these drugs. Thus, there is a need for additional effective LDL-C reducing agents.

Areas covered: Evolocumab (AMG145) is a monoclonal antibody inhibiting the proprotein convertase subtilisin/kexin type 9 that binds to the liver LDL receptor and prevents it from normal recycling by targeting it for degradation. Phase I and II trials revealed that its subcutaneous injection, either alone or in combination with statins, is able to reduce LDL-C from 40 to 80%, apolipoprotein B100 from 30 to 59% and lipoprotein(a) from 18 to 36% in a dose-dependent manner. The incidence of side effects seems to be low and mainly limited to nasopharyngitis, injection site pain, arthralgia and back pain.

Expert opinion: Evolocumab is an innovative powerful lipid-lowering drug, additive to statins and with an apparently large therapeutic range associated to a low rate of mild adverse events. If available data will be confirmed in long-term trials with strong outcomes, Evolocumab will provide an essential tool to treat high-risk patients who need to reach ambitious LDL-C target.

Keywords: AMG145; hypercholesterolemia; lipid-lowering drugs; proprotein convertase subtilisin/kexin type 9.