Praluent is a PCSK9 (proprotein convertase
subtilisin/kexin type 9) inhibitor indicated as adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or clinical atherosclerotic CVD, who require additional lowering of LDL cholesterol.
Like evolocumab, another PCSK9 inhibitor under FDA review, alirocumab is a human monoclonal antibody that binds to PCSK9 (proprotein convertase
subtilisin kexin type 9), a serine protease that reduces the number of receptors on the liver that remove LDL cholesterol from the blood.
In the past 2 and a half decades, 9 members of the proprotein convertase
subtilisin/kexin (PCSK)  have been identified in mammals, with broad substrate specificities.
Of these segments, anti-hypertensives and cholesterol-lowering drugs are emerging as the most promising therapy class owing to the development of drugs targeting proprotein convertase
subtilisin/kexin type 9 (PCSK9) and cholesteryl ester transfer protein (CETP).
ALN-PCS is a systemically delivered RNAi therapeutic targeting the gene proprotein convertase
subtilisin/kexin type 9, or PCSK9, a target validated by human genetics that is involved in the metabolism of low-density lipoprotein cholesterol (LDL-C, or "bad" cholesterol).
OSLER (Open-Label Study of Long-Term Evaluation Against LDL Cholesterol) included 4,465 patients who had completed one of a dozen earlier phase II or III studies of evolocumab, a monoclonal antibody that inhibits proprotein convertase
subtilisin kexin type 9 (PCSK9), and were then randomized 2:1 to 1 year of open-label evolocumab administered subcutaneously at either 140 mg every 2 weeks or 420 mg once monthly plus standard lipid lowering, or to standard lipid lowering alone, generally with moderate- or highdose statins.
Disruption of proprotein convertase
1/3 (PC1/3) expression in mice causes innate immune defects and uncontrolled cytokine secretion.
Combinatorial Environmental Stress and Subtilisin-like Proprotein Convertase
Persons with genetically lifelong low LDL-C levels--resulting from hypobetalipoproteinaemia or loss-of-function mutations in the proprotein convertase
subtilisin/kexin type 9 (PCSK9) gene--have a markedly reduced risk (80-90%) of developing CAD, despite a similar prevalence of other CVD risk factors.
SAR236553/REGN727 is a potential first-in-class, subcutaneously administered, fullyhuman antibody that lowers low-density lipoprotein (LDL) cholesterol by targeting PCSK9 (proprotein convertase
subtilisin/kexin type 9), an enzyme which binds LDL receptors, leading to their accelerated degradation and increased LDL-cholesterol (LDL-C) levels.
Recently, a third gene, proprotein convertase
subtilisin/ kexin type 9 (PCSK9), causing autosomal dominant hypercholesterolemia Type 3 (OMIN 603776) has been described.
The program, in collaboration with University of Texas (UT) Southwestern Medical Center at Dallas, is focused on evaluating new approaches for reducing LDL cholesterol levels using RNAi therapeutics directed to the disease target called proprotein convertase
subtilisn/kexin type 9, or PCSK9.