Last update: March 2019
Praluent is a fully human monoclonal antibody1 that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) from binding to LDL receptors (LDLR), increasing the number of LDLRs available to remove LDL-C from the circulation1,2 (Figure 1).
Figure 1. Praluent mechanism of lipid lowering
LDL-C levels in the blood are affected by three main mechanisms3 (Figure 2)
- Internal absorption of dietary cholesterol
- De novo cholesterol synthesis
- Clearance of LDL-C by LDLR in the liver
Cholesterol lowering drugs work via these mechanisms (Figure 2)
- Statins inhibit HMGCoA reductase which decreases de novo cholesterol synthesis leading to a 40–60% reduction in LDL-C3
- Ezetimibe blocks the NPC1L1 protein reducing dietary cholesterol absorption and leading to a reduction in LDL-C of 15–20%3,4
- Praluent, a PCSK9 inhibitor, stops PCSK9 from binding to the LDLR, which prevents LDLR degradation and increases the number of LDLR available to clear LDL-C1. Praluent, on top of maximally tolerated statin therapy with or without other lipid-lowering therapy reduces LDL-C by up to 61% (-1.92mmol/L from baseline with 150 mg Q2W)5
- The usual starting dose for Praluent is 75 mg administered subcutaneously once every 2 weeks. Patients requiring larger LDL-C reduction (>60%) may be started on 150 mg once every 2 weeks, or 300 mg once every 4 weeks (monthly), administered subcutaneously.
Figure 2: Mechanisms of lipid lowering [Adapted from Grundy SM (2016)3]
Watch this video to learn about Praluent’s mechanism of action
- Praluent Summary of Product Characteristics. Available at https://www.medicines.org.uk/emc/medicine/30956. Accessed March 2019.
- Poirier S and Mayer G. The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol. Drug Des Devel Ther 2013; 7:1135–48.
- Grundy, SM. Dyslipidaemia in 2015: Advances in treatment of dyslipidaemia. Nat Rev Cardiol 2016; 13:74-5.
- Phan B et al. Ezetimibe therapy: mechanism of action and clinical update. Vasc Health Risk Manag 2012; 8:415–27
- Robinson JG et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. NEJM 2015; 372:1489–99