Repatha® helps the liver clear LDL cholesterol by limiting the actions of a protein called PCSK9—and less PCSK9 means less LDL-C in the blood.1
Via inhibition of HMG-CoA reductase, statins reduce the production of plasma cholesterol and lipoprotein.2
By inhibiting PCSK9, Repatha® increases the number of LDL-C receptors on the surface of the liver, resulting in reduction of LDL-C from circulation.1
Repatha® mechanism of action1
What is PCSK9?
PCSK9 is a protein that promotes degradation of low density lipoprotein receptors (LDLRs). This results in fewer LDLRs on the liver cell surface, increasing plasma LDL-C levels.
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Why Repatha® inhibits PCSK9
By inhibiting the binding of PCSK9 to LDLR, Repatha® permits LDLRs to recycle back to the liver cell surface. This, in turn, increases the number of LDLRs available to clear LDL-C from the blood, thereby lowering LDL-C levels.
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How Repatha® lowers LDL-C levels
Repatha® lowers LDL-C levels by inhibiting PCSK9, increasing the number of LDLRs on the hepatocyte surface, thereby resulting in lower LDL-C plasma concentrations.
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What is PCSK9?
Why Repatha® inhibits PCSK9
How Repatha® lowers LDL-C levels
References: 1. Repatha® (evolocumab) prescribing information, Amgen. 2. Lipitor® (atorvastatin) prescribing information, Pfizer Inc.
CVD = cardiovascular disease; LDL-C = low-density lipoprotein cholesterol; MI = myocardial infarction.
LDL-C = low-density lipoprotein cholesterol; MI = myocardial infarction.
ACS = acute coronary syndrome; LDL-C = low-density lipoprotein cholesterol; MI = myocardial infarction; PCSK9 = proprotein convertase subtilisin/kexin type 9.
Reference: 1. Repatha® (evolocumab) prescribing information, Amgen.
Contraindication: Repatha® is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in Repatha®. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha®.
Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema, have been reported in patients treated with Repatha®. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with Repatha®, treat according to the standard of care, and monitor until signs and symptoms resolve.
Adverse Reactions in Primary Hyperlipidemia: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.
From a pool of the 52-week trial and seven 12-week trials: Local injection site reactions occurred in 3.2% and 3.0% of Repatha®-treated and placebo-treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising. Hypersensitivity reactions occurred in 5.1% and 4.7% of Repatha®-treated and placebo-treated patients, respectively. The most common hypersensitivity reactions were rash (1.0% versus 0.5% for Repatha® and placebo, respectively), eczema (0.4% versus 0.2%), erythema (0.4% versus 0.2%), and urticaria (0.4% versus 0.1%).
Adverse Reactions in the Cardiovascular Outcomes Trial: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: diabetes mellitus (8.8% Repatha®, 8.2% placebo), nasopharyngitis (7.8% Repatha®, 7.4% placebo), and upper respiratory tract infection (5.1% Repatha®, 4.8% placebo).
Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was 8.1% in patients treated with Repatha® compared with 7.7% in patients that received placebo.
Immunogenicity: Repatha® is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity with Repatha®.
Please see full Prescribing Information.
IMPORTANT SAFETY INFORMATION
Contraindication: Repatha® is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in Repatha®. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha®.
Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema, have been reported in patients treated with Repatha®. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with Repatha®, treat according to the standard of care, and monitor until signs and symptoms resolve.
Adverse Reactions in Primary Hyperlipidemia: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.
From a pool of the 52-week trial and seven 12-week trials: Local injection site reactions occurred in 3.2% and 3.0% of Repatha®-treated and placebo-treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising. Hypersensitivity reactions occurred in 5.1% and 4.7% of Repatha®-treated and placebo-treated patients, respectively. The most common hypersensitivity reactions were rash (1.0% versus 0.5% for Repatha® and placebo, respectively), eczema (0.4% versus 0.2%), erythema (0.4% versus 0.2%), and urticaria (0.4% versus 0.1%).
Adverse Reactions in the Cardiovascular Outcomes Trial: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: diabetes mellitus (8.8% Repatha®, 8.2% placebo), nasopharyngitis (7.8% Repatha®, 7.4% placebo), and upper respiratory tract infection (5.1% Repatha®, 4.8% placebo).
Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was 8.1% in patients treated with Repatha® compared with 7.7% in patients that received placebo.
Immunogenicity: Repatha® is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity with Repatha®.
Please see full Prescribing Information.
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