WHAT IS REPATHA®?


Repatha® is a human monoclonal IgG2 directed against human PCSK9. Repatha® binds to PCSK9 and inhibits circulating PCSK9 from binding to the low density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha® increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.1


Indication

Repatha® is indicated as adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (CVD), who require additional lowering of low density lipoprotein cholesterol (LDL-C).

Limitations of Use

The effect of Repatha® on cardiovascular morbidity and mortality has not been determined.

Repatha® Mechanism of Action

How Repatha® Works

How Repatha worksHow Repatha works
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PCSK9 PROMOTES LDL RECEPTOR (LDLR) DEGRADATION2

  • PCSK9 is a protein that promotes degradation of LDLRs. This results in fewer LDLRs on the liver cell surface, increasing plasma LDL-C levels2

REPATHA® INHIBITS PCSK9, THEREBY PREVENTING LDLR DEGRADATION1



  • By inhibiting the binding of PCSK9 to LDLR, Repatha® permits LDLRs to recycle back to the liver cell surface1
  • This in turn increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels1

How Repatha® impacts LDL-C levels

PCSK9 INHIBITION WITH REPATHA®

How Repatha works 

  • Repatha® lowers LDL-C levels by inhibiting PCSK9, increasing the number of LDLRs on the hepatocyte surface, thereby resulting in lower LDL-C plasma concentrations1

References:

  1. Repatha® (evolocumab) Prescribing Information, Amgen.
  2. Qian Y-W, Schmidt RJ, Zhang Y, et al. J Lipid Res. 2007;48:1488-1498.
IMPORTANT SAFETY INFORMATION
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IMPORTANT SAFETY INFORMATION

Contraindication: Repatha® is contraindicated in patients with a history of a serious hypersensitivity reaction to Repatha®.

Allergic reactions: Hypersensitivity reactions (e.g. rash, urticaria) have been reported in patients treated with Repatha®, including some that led to discontinuation of therapy. If signs or symptoms of serious allergic reactions occur, discontinue treatment with Repatha®, treat according to the standard of care, and monitor until signs and symptoms resolve.

Adverse reactions: The most common adverse reactions (> 5% of Repatha®-treated patients and more common than placebo) were: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.

In a 52-week trial, adverse reactions led to discontinuation of treatment in 2.2% of Repatha®-treated patients and 1% of placebo-treated patients. The most common adverse reaction that led to Repatha® treatment discontinuation and occurred at a rate greater than placebo was myalgia (0.3% versus 0% for Repatha® and placebo, respectively).

Adverse 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. The proportions of patients who discontinued treatment due to local injection site reactions in Repatha®-treated patients and placebo-treated patients were 0.1% and 0%, respectively.

Allergic reactions occurred in 5.1% and 4.7% of Repatha®-treated and placebo-treated patients, respectively. The most common allergic 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%).

Neurocognitive events were reported in less than or equal to 0.2% in Repatha®-treated and placebo-treated patients.

In a pool of placebo- and active-controlled trials, as well as open-label extension studies that followed them, a total of 1,988 patients treated with Repatha® had at least one LDL‑C value < 25 mg/dL. Changes to background lipid-altering therapy were not made in response to low LDL-C values, and Repatha® dosing was not modified or interrupted on this basis. Although adverse consequences of very low LDL-C were not identified in these trials, the long-term effects of very low levels of LDL-C induced by Repatha® are unknown.

Musculoskeletal adverse reactions were reported in 14.3% of Repatha®-treated patients and 12.8% of placebo-treated patients. The most common adverse reactions that occurred at a rate greater than placebo were back pain (3.2% versus 2.9% for Repatha® and placebo, respectively), arthralgia (2.3% versus 2.2%), and myalgia (2.0% versus 1.8%).

Immunogenicity: Repatha® is a human monoclonal antibody. As with all therapeutic proteins, there is a potential for immunogenicity with Repatha®.

INDICATION

Repatha® is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (CVD), who require additional lowering of low density lipoprotein cholesterol (LDL-C).

The effect of Repatha® on cardiovascular morbidity and mortality has not been determined.

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