PCSK9 mAb (alirocumab) — The LDL-C Lowering Antibody
Alirocumab is a monoclonal antibody that profoundly lowers LDL cholesterol by inhibiting the PCSK9 protein. By drastically reducing atherogenic lipoproteins, it directly targets cardiovascular disease, which is the leading cause of age-related mortality globally.
Mechanism of Action
Alirocumab is a fully human monoclonal antibody that binds to proprotein convertase subtilisin/kexin type 9 (PCSK9). By inhibiting PCSK9, it prevents the degradation of low-density lipoprotein receptors (LDLRs) on the surface of hepatocytes. This leads to an increased number of LDLRs available to clear circulating LDL-C, resulting in profoundly lowered plasma LDL-C levels. Lowering LDL-C is a primary strategy for reducing atherosclerotic cardiovascular disease risk, a major driver of age-related mortality.
Human Trial Evidence
The ODYSSEY OUTCOMES trial (2018) demonstrated that alirocumab significantly reduced the risk of major adverse cardiovascular events (MACE) and all-cause mortality in patients with a recent acute coronary syndrome. It is highly effective at lowering LDL-C levels in humans.
Dosing Protocol
75 mg or 150 mg administered subcutaneously once every 2 weeks, or 300 mg once every 4 weeks. Prescription required.
Safety & Contraindications
Common adverse effects include injection site reactions, nasopharyngitis, and influenza. Rare but serious risks include hypersensitivity reactions. Prescription required. Long-term safety is generally well-established, though very low LDL-C levels require monitoring.