Repatha® Has an Established Safety Profile With More Than 16,000 Patients Studied1,2

  • In a 52-week controlled trial, adverse reactions led to discontinuation of treatment in 2.2% of Repatha®-treated patients and 1.0% 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)1

  • In seven pooled 12-week controlled trials, adverse reactions led to discontinuation of treatment in 1.7% of Repatha®-treated patients and 1.7% of placebo-treated patients2

*Repatha® 420 mg once monthly.

Includes erythema, pain, or bruising.

Repatha® 140 mg every two weeks and 420 mg once monthly.

A phase 3, double-blind, randomized, placebo-controlled, parallel-group, multicenter study of Repatha® in patients with clinically evident CV disease on optimized statin therapy.


A total of 27,564 subjects ages 40 to 85 years were randomized in this study and entered a 1:1 randomization to receive either placebo or Repatha®.2


Repatha® every 2 weeks or once monthly + a statin lowered LDL-C by 59% compared to a statin alone. Patients in the Repatha® arm achieved a median LDL-C of 30 mg/dL. Baseline LDL-C for both arms was 92 mg/dL.


Optimized statin therapy was defined as preferably a high-intensity statin but must have been at least atorvastatin at a dose of 20 mg daily or its equivalent, with or without ezetimibe.

*Patients were exposed to Repatha® or placebo for a median 24.1 months.5

The between-group difference was nominally significant (P<0.001).

The total numbers of patients were 8337 in the evolocumab group and 8339 in the placebo group, because patients with prevalent diabetes at the start of the trial were excluded.

Safety In Patients With Low LDL-C Levels1,4

  • 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/dL1

  • 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 basis1

  • 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 unknown1

An integrated analysis of phase 2 and 3 randomized placebo and active controlled studies of Repatha® for up to 52 weeks duration4

SoC = Standard of Care.

  • The EBBINGHAUS study showed that the effect of Repatha® on the primary endpoint of executive function was non-inferior to placebo.5

    • There was no signal for worsening cognitive function observed even in an exploratory analysis of patients who reached LDL cholesterol below 25 mg/dL.5

In addition, there was no statistical difference between Repatha® and placebo on the other cognitive domains tested: working memory, memory function and psychomotor speed (secondary endpoints).5

The EBBINGHAUS study was a substudy of the larger Repatha Long Term Study (N=27,564) of patients with clinically-evident CV disease on a background of optimized statin therapy. EBBINGHAUS followed 1,204 patients over a median of 19.8 months.5

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References: 1. Repatha® (evolocumab) Prescribing Information, Amgen. 2. Sabatine MS, Giugliano RP, Keech AC, et al. N Engl J Med. 2017. DOI: 10.1056/NEJMoal615664. 3. Data on file, Amgen; 2015. 4. Amgen EMDAC Briefing Document 2015. 5. Giugliano R. EBBINGHAUS: A Cognitive Study of Patients Enrolled in the FOURIER Trial. Presented at: The 66th Annual American College of Cardiology Convention: 2017 March 10-12; Washington DC.

IMPORTANT SAFETY INFORMATION

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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 been published. Inclusion of the results in the approved labeling is under evaluation with the FDA.

Please see full Prescribing Information.

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