Repatha® Clinical Trials | Repatha® (evolocumab)

Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk

Repatha^® added to a statin was studied in established CVD patients who were at risk for CV events¹

Explore the FOURIER study, a large CV outcomes trial that helped to inform the latest AHA/ACC Guideline^1,2

27564

patients

with established CVD and LDL-C ≥70 mg/dL and/or non-HDL-C ≥100 mg/dL despite high- or moderate-intensity statin therapy¹

STUDY DESIGN

27,564 patients

with established CVD and LDL-C ≥70 mg/dL and/or non-HDL-C ≥100 mg/dL despite high- or moderate-intensity statin therapy¹

FOURIER was a double-blind, randomized, placebo-controlled, even-driven trial¹

Patients received either subcutaneous injections of Repatha^® (140 mg every 2 weeks or 420 mg once monthly) or placebo¹

Patients on stable background lipid-lowering therapy had a median baseline LDL-C of 92 mg/dL¹

Patients were aged ≥40 to ≤85 years

with prior MI, stroke, or symptomatic PAD^3,*

92 mg/dL LDL-C

median baseline for enrolled patients¹

81%

of patients had previously experienced ≥1 MI¹

99%

of patients were receiving high- or moderate-intensity statin therapy¹

70%

of patients in the Repatha^® arm were on high-intensity statins³

*Symptomatic peripheral arterial disease (history of claudication with ABI <0.85 or previous revascularization or amputation).²

Count on Repatha^® for your patients who need more to achieve ACC/AHA guideline-recommended LDL-C <70 mg/dL^1,2

Adding Repatha^® to a statin can dramatically lower LDL-C in just 4 weeks³

Repatha^® + statin lowered LDL-C by an average of

63%

in 12 weeks¹

of patients achieved LDL-C ≤70 mg/dL at 48 weeks³

ADD REPATHA^® NOW TO PROVIDE SUSTAINED LDL-C REDUCTION¹

For patients with established CVD

REPATHA^® ADDED TO A STATIN REDUCED THE RISK OF CV EVENTS MORE THAN STATINS ALONE¹

Repatha^® added to a statin was proven to reduce the risk of composite CV events by 20%
in a median of only 2.2 years, and the benefit improved over time^1,3

Key secondary composite endpoint of time to first occurrence of CV death, MI, or stroke

HR 0.80 (95% CI, 0.73-0.88; P < 0.0001) ARR = 2.0%^1,3

• Primary composite endpoint of time to first occurrence of CV death, MI, hospitalization for unstable angina, stroke or coronary revascularization: HR 0.85 (95% CI, 0.79-0.92; P < 0.0001)¹

MI: 27% RRR¹

Revascularization: 22% RRR¹

Stroke: 21% RRR¹

• Relative risk reductions for the primary and secondary composite endpoints were driven by a reduction in the risk of Ml: HR 0.73 (95% Cl, 0.65-0.82); stroke: HR 0.79 (95% Cl, 0.66-0.95); and coronary revascularization: HR 0.78 (95% Cl, 0.71-0.86)^1,*

Observed HR for CV death: 1.05 (95% Cl, 0.88-1.25) and hospitalizations due to unstable angina: 0.99 (95% Cl, 0.82-1.18).¹

*Not statistically signiﬁcant

FOURIER subanalysis: recent MI

HELP PREVENT ANOTHER MI: PATIENTS WITHIN 1 YEAR OF THEIR MOST RECENT MI HAVE A HIGHER CV RISK^4-6

In a FOURIER subanalysis, statin + Repatha^® provided greater AAR for patients who suffered an MI within 1 year compared to patients with a more distant MI⁴

In a FOURIER subanalysis, statin + Repatha^® provided greater ARR for patients who suffered an MI within 1 year compared to patients with a more distinct MI⁴

RECENT MI

Key secondary composite endpoint of time to first occurrence of CV death, MI, or stroke⁴

HR 0.75 (95% CI, 0.62-0.91) (n = 5,711)

For recent MI patients ARR = 3.2%⁴

For distant MI patients ARR = 1.3%⁴

• ARR of 2.0% in the overall Repatha^® CV Outcomes Trial study population was evaluated at 36 months³

• Analysis of 81% (N = 22,320) of patients in Repatha^® CV Outcomes Trial with a prior MI⁴

• 5,711 patients who experienced an MI within 1 to 12 months of randomization were compared to 16,609 patients with a more distant MI (more than 12 months prior to randomization)⁴

Observed HR for CV death: 1.05 (95% CI, 0.88-1.25) from the primary analysis¹

FOURIER subanalysis: target LDL-C levels

AHA/ACC- & ESC/EAS- RECOMMENDED LDL-C LEVELS WERE ACHIEVED FOR MOST PATIENTS^2,4,7

FOURIER subanalysis: target LDL-C levels

AHA/ACC- & ESC/EAS-RECOMMENDED LDL-C LEVELS WERE ACHIEVED FOR MOST PATIENTS^2,4,7

Achievement of guideline-recommended LDL-C levels at 4 weeks in patients with recent MI (≤12 months)⁴

LDL-C ≤40 mg/dL

ESC/EAS Guideline for patients experiencing second event within 2 years⁷

FOURIER subanalysis: target LDL-C levels

AHA/ACC- & ESC/EAS-RECOMMENDED LDL-C LEVELS WERE ACHIEVED FOR MOST PATIENTS^2,4,7

Achievement of guideline-recommended LDL-C levels at 4 weeks in patients with recent MI (≤12 months)⁴

LDL-C ≤55 mg/dL

ESC/EAS Guideline⁷

FOURIER subanalysis: target LDL-C levels

AHA/ACC- & ESC/EAS-RECOMMENDED LDL-C LEVELS WERE ACHIEVED FOR MOST PATIENTS^2,4,7

Achievement of guideline-recommended LDL-C levels at 4 weeks in patients with recent MI (≤12 months)⁴

LDL-C ≤70 mg/dL

AHA/ACC Guideline²

FOURIER post-hoc subanalysis: patients with prior PCI

REPATHA^® ADDED TO A STATIN REDUCED MAJOR CV EVENTS^* IN PATIENTS WITH A PRIOR PCI⁸

Repatha^® + a statin provided a greater ARR in ASCVD patients with prior PCI compared to those without PCI^8,9

*Major CV events were the composite of coronary death, MI, or coronary revascularization.

FOURIER post-hoc subanalysis: patients with prior PCI

REPATHA^® ADDED TO A STATIN REDUCED MAJOR CV EVENTS^* IN PATIENTS WITH A PRIOR PCI⁸

Repatha^® + a statin provided a greater ARR in ASCVD patients with prior PCI compared to those without PCI^8,9

Prior PCI | ARR = 2.8%⁹

No Prior PCI | ARR = 0.3%⁹

• ARR of 2.0% in the overall Repatha^® CV Outcomes Trial study population was demonstrated at 36 months³

• Analysis of 62% (N = 17,073) of patients with prior PCI in Repatha^® CV Outcomes Trial⁹

• Comparison of 17,073 patients with prior PCI versus 10,455 patients without prior PCI in the Repatha^® and placebo arms of the Repatha^® CV Outcomes Trial⁸

• Observed HR for CV death in the primary analysis: 1.05 (95% CI, 0.88-1.25)¹

• Post hoc analyses are exploratory and no statistical conclusions can be drawn

* Major CV events were the composite of coronary death, MI, or coronary revascularization.⁹

Outcomes by baseline LDL-C

REGARDLESS OF BASELINE LDL-C, REPATHA^® ADDED TO A STATIN CONSISTENTLY REDUCED THE RISK OF COMPOSITE CV EVENTS¹⁰

Outcomes by baseline LDL-C

REGARDLESS OF BASELINE LDL-C LEVEL, REPATHA^® ADDED TO A STATIN CONSISTENTLY REDUCED THE RISK OF COMPOSITE CV EVENTS¹⁰

Key secondary endpoint: composite of CV death, MI, or stroke¹⁰

THE SAFETY PROFILE OF REPATHA^® HAS BEEN DEMONSTRATED IN OVER 27,000 PATIENTS^1,*

*In the CV outcomes trial (patients randomized to Repatha^® or placebo)

The Repatha^® CV Outcomes Trial demonstrated the long-term safety of Repatha^® added to a statin over a median of 2.2 years³

THE SAFETY PROFILE OF REPATHA^® HAS BEEN DEMONSTRATED IN OVER 27,000 PATIENTS^1,*

The Repatha^® CV Outcomes Trial demonstrated the long-term safety of Repatha^® added to a statin over a median of 2.2 years³

Repatha^® CV Outcomes Trial: Adverse events and Laboratory test results^1,3,10

AHA/ACC = American Heart Association/American College of Cardiology; ARR = absolute risk reduction; ASCVD = atherosclerotic cardiovascular disease; CI = confidence interval; CV = cardiovascular; CVD = cardiovascular disease; ESC/EAS = European Society of Cardiology/European Atherosclerosis Society; HDL-C = high-density lipoprotein cholesterol; HR = hazard ratio; LDL-C = low-density lipoprotein cholesterol; MI = myocardial infarction; PAD = peripheral artery disease; PCI = percutaneous coronary intervention; RRR = relative risk reduction;

REFERENCES:

1. Repatha^® (evolocumab) prescribing information, Amgen. 2. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73:e285-e350. 3. Sabatine MS, Giugliano RP, Keech AC, et al. FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713-1722. 4. Gencer B, Mach F, Murphy SA, et al. Efﬁcacy of evolocumab on cardiovascular outcomes in patients with recent myocardial infarction: a prespeciﬁed secondary analysis from the FOURIER trial. JAMA Cardiol. May 20, 2020:e200882. 5. Wang Y, Li J, Zheng X et al. Risk factors associated with major cardiovascular events 1 year after acute myocardial infarction. JAMA Netw Open. 2018;1:e181079. 6. Jernberg T, Hasvold P, Henriksson M, Hjelm H, Thuresson M, Janzon M. Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J. 2015;36:1163-1170. 7. Mach F, Baigent C, Catapano AL, et al; ESC Scientiﬁc Document Group. 2019 ESC EAS guidelines for the management of dyslipidaemias: lipid modiﬁcation to reduce cardiovascular risk. Eur Heart J. 2020;47:111-188. 8. Furtado RHM, Fagundes AA, Oyama K, et al. Effects of evolocumab in patients with prior percutaneous coronary intervention: an analysis from the Fourier trial. Presented at: American Heart Association Scientific Sessions 2020; November 13-17, 2020. 9. Furtado RH, Fagundes AA, Oyama K, et al. Effects of evolocumab in patients with prior percutaneous coronary intervention: an analysis from the Fourier trial. Circulation. 2020;142:A16688. 10. Data on ﬁle, Amgen; 2017.

Primary Study Overview

Study Design

Patient Characteristics

LDL-C Reductions

CV Outcomes

Recent MI

Guideline LDL-C Levels

PCI Subanalysis

Baseline LDL-C Subgroup Analysis

FOURIER Safety

Glossary & References

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INDICATIONS

Repatha^® is indicated:

In adults with established cardiovascular disease to reduce the risk of myocardial infarction, stroke, and coronary revascularization
As an adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH) to reduce LDL C

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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Important Safety Information

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

Please see full Prescribing Information.