Alirocumab: A Review in Hypercholesterolemia

Alirocumab (Praluent(A (R))) is a monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) that is administered via subcutaneous injection every 2 weeks. Across ten phase III studies from the ODYSSEY clinical trial program in patients with heterozygous familial hypercholesterolemia (heFH) or nonfamilial hypercholesterolemia (nonFH), including some with mixed dyslipidemia, subcutaneous alirocumab 75 or 150 mg every 2 weeks was significantly more effective with regard to reducing low-density lipoprotein-cholesterol (LDL-C) over 24 weeks than comparator agents (i.e. matching placebo, once-daily oral ezetimibe, or modified oral statin therapy), including when administered as monotherapy or in combination with statin therapy, and when administered with non-statin lipid-lowering therapy (LLT) in patients with statin intolerance. Alirocumab provided sustained LDL-C-lowering efficacy over 52-78 weeks' treatment in longer-term trials, and was associated with significantly favorable effects on several other lipid parameters, including non-high-density lipoprotein-cholesterol (non-HDL-C) and lipoprotein (a) [Lp(a)]. Alirocumab was generally well tolerated in phase III trials, with no apparent increase in muscle-related adverse events compared with placebo. Thus, alirocumab is a valuable emerging option for use in patients with hypercholesterolemia, particularly patients with statin intolerance or inadequately-controlled LDL-C despite statin therapy; however, more data are needed to establish its potential cardiovascular benefits.