Despite the proven efficacy of
statins, they often fail to achieve
low-density lipoprotein (
LDL) cholesterol goals, especially in high-risk patients. Moreover, a large number of subjects cannot tolerate
statins or full doses of these drugs, in particular patients with
familial hypercholesterolemia. Thus, there is a need for additional effective
LDL cholesterol-
reducing agents.
Evolocumab (AMG145) is a
monoclonal antibody inhibiting
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, II, and III trials revealed that, on
subcutaneous injection, either alone or in combination with
statins,
evolocumab is able to reduce high
LDL cholesterol levels from 54% to 80%,
apolipoprotein B100 from 31% to 61%, and
lipoprotein(a) from 12% 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.
Evolocumab is an innovative powerful
lipid-lowering drug, additive to
statins and/or
ezetimibe, with a large therapeutic range associated with a low rate of mild adverse events. If the available data are confirmed in long-term trials with strong outcome measures,
evolocumab will become an essential tool in the treatment of a large number of high-risk patients, such as those affected by
familial hypercholesterolemia, those who are unable to tolerate an efficacious
statin dosage, and those at very high cardiovascular risk and unable to achieve their target
LDL cholesterol levels with currently available
lipid-lowering
therapies.