evolocumab

Evolocumab is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). By binding PCSK9, evolocumab prevents PCSK9 from degrading LDL receptors on hepatocytes, increasing receptor recycling and uptake of low-density lipoprotein cholesterol (LDL-C) from the blood. It is marketed under the brand name Repatha and is developed and manufactured by Amgen.

Indications and use: Evolocumab is used as an adjunct to diet, with or without other lipid-lowering therapies, to reduce LDL-C in adults with primary hyperlipidemia or familial hypercholesterolemia and in adults and certain pediatric patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease to reduce cardiovascular risk. It is also approved for pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia. Dosing is by subcutaneous injection: 140 mg every two weeks or 420 mg once monthly, with adjustments based on LDL-C response and tolerability.

Efficacy and safety: Evolocumab can lower LDL-C by up to about 60% from baseline and may also reduce non-HDL cholesterol and apolipoprotein B. In cardiovascular risk reduction trials in adults with ASCVD, it reduced the incidence of major adverse cardiovascular events. Common adverse effects include injection-site reactions, back pain, flu-like symptoms, and upper respiratory infections. Rare hypersensitivity reactions and neurocognitive effects have been reported. Safety in pregnancy is not well established, and use during pregnancy should be guided by risk-benefit considerations.

Regulatory status: Evolocumab has been approved in many jurisdictions for the treatment of hyperlipidemia and for reduction of cardiovascular risk in adults with ASCVD, as well as approved indications for certain pediatric patients. As with other biologics, patients should be monitored for lipid response and potential adverse effects, and concomitant lipid-lowering therapy should be considered.