Drug Overview
Repatha (evolocumab; Amgen/Astellas) is a fully human monoclonal immunoglobulin G2 antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protease involved in the intracellular and extracellular regulation of low-density lipoprotein receptor (LDLR) expression. It binds to the LDLR and targets it for lysosomal degradation within the hepatocytes. PCSK9 is also known to increase the production of apolipoprotein B-containing lipoproteins. Evolocumab prevents circulating PCSK9 from binding to the epidermal growth factor-like repeat A domain, its target on the LDLR. This consequently inhibits LDLR degradation, allowing the LDLRs to be recycled to the cell surface, thereby increasing plasma clearance of low-density lipoprotein cholesterol.
Repatha’s sales have been much lower than expected since its launch in 2015. At a list price of over $14,000 per patient per year, payers have implemented strict reimbursement protocols in order to restrict the PCSK9 inhibitor’s use to only the most high-risk dyslipidemia patients. The substantial reductions in cardiovascular (CV) risk in comparison to current lipid-lowering therapies in its Phase III CV outcomes trial, FOURIER, will play a crucial role in helping Amgen to justify the high cost of Repatha.
Repatha (evolocumab; Amgen/Astellas) is a fully human monoclonal immunoglobulin G2 antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protease involved in the intracellular and extracellular regulation of low-density lipoprotein receptor (LDLR) expression. It binds to the LDLR and targets it for lysosomal degradation within the hepatocytes. PCSK9 is also known to increase the production of apolipoprotein B-containing lipoproteins. Evolocumab prevents circulating PCSK9 from binding to the epidermal growth factor-like repeat A domain, its target on the LDLR. This consequently inhibits LDLR degradation, allowing the LDLRs to be recycled to the cell surface, thereby increasing plasma clearance of low-density lipoprotein cholesterol.
Repatha’s sales have been much lower than expected since its launch in 2015. At a list price of over $14,000 per patient per year, payers have implemented strict reimbursement protocols in order to restrict the PCSK9 inhibitor’s use to only the most high-risk dyslipidemia patients. The substantial reductions in cardiovascular (CV) risk in comparison to current lipid-lowering therapies in its Phase III CV outcomes trial, FOURIER, will play a crucial role in helping Amgen to justify the high cost of Repatha.
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