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 in Primary Hyperlipidemia, including HeFH: The most common adverse reactions (> 5% of Repatha®-treated patients and occurring more frequently than placebo) in clinical trials in primary hyperlipidemia (including HeFH) 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).

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%).

Adverse reactions in the Cardiovascular Outcomes trial: The safety profile of Repatha® in this trial was generally consistent with the safety profile described above in the 12- and 52-week controlled trials involving patients with primary hyperlipidemia (including HeFH). Serious adverse events occurred in 24.8% and 24.7% of Repatha®-treated and placebo-treated patients, respectively. Adverse events led to discontinuation of study treatment in 4.4% of patients assigned to Repatha® and 4.2% assigned to placebo. Common adverse reactions (>5% of patients treated with Repatha® and occurring more frequently than placebo) included 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 assigned to Repatha® compared with 7.7% in those assigned to placebo.

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

Please see full Prescribing Information.

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