PROFICIO...CV Outcomes CV Outcomes Jean-Baptiste Joseph Fourier 1768 – 1830 Fourier demonstrated how the conduction of heat in solid bodies may be analyzed in terms of the infinite

Evolocumab PROFICIO Program

PROFICIOEst. 2011

PROFICIO is derived from the Latin word that means “to go forward, advance, make progress.”

PROFICIO is Amgen’s program of clinical studies investigating the impact of evolocumab on cardiovascular disease across multiple patient populations. Inspired by the work of scientific pioneers throughout history, each trial in PROFICIO is named after a revolutionary scientist. Over 38,000 subjects across 36 trials have been studied.

PROFICIO GALLERYProgram to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations

Japanese/Asian• YUKAWA-2 (N = 409)

Statin IntoleranceGAUSS-4 (N = 61)

Secondary PreventionFOURIER OLE (N = 5,037)

Secondary Prevention FOURIER OLE in select EU countries (N = 1,600)


Pediatrics• HAUSER OLE (N = 115)

Safety OSLER-2 (N = 3,681)

SPECIALPOPULATIONS

CV OUTCOMES

CONSISTENT LDL-C EFFECT

FAMILIALHYPERCHOLESTEROLEMIA

LONG-TERM

IMAGINGPlaque GLAGOV OLE (N = 770)

Year reflects start of study. Highlighted studies are featured in this booklet.

2011 2012 2013 2014 2015 2016 2017 2018 2019Secondary Prevention FOURIER (N = 27,564)

Combination Therapy LAPLACE (N = 631)

High CV Risk Without Prior MI or Stroke VESALIUS- CV (N ~13,000)

Monotherapy MENDEL (N = 411)

Statin IntoleranceGAUSS (N = 160)

Monotherapy MENDEL-2 (N = 615)

Self-administration THOMAS-1 (N = 149)THOMAS-2 (N = 164)

Lipoprotein Kinetics• FLOREY (N = 89)

Safety OSLER (N = 1,324)

Efficacy DESCARTES (N = 905)

NeurocognitionEBBINGHAUS (N = 1974)

Plaque GLAGOV (N = 970)

Plaque HUYGENS (N = 150)

Arterial wall inflammation• ANITSCHKOW (N = 129)

Heterozygous FH RUTHERFORD (N = 168)

Heterozygous and Homozygous FH TAUSSIG (N = 300)

Homozygous FH TESLA (N = 58)

Pediatrics• HAUSER RCT (N = 150)

Apheresis• DeLAVAL (N = 39)

Homozygous FH• RAMAN (N = 30)

Diabetes• BANTING (N = 424)HIV

• BEIJERINCK (N = 467)

Diabetes• BERSON (N = 986)Japanese/Asian

• YUKAWA (N = 310)

Combination Therapy LAPLACE-2 (N = 2,067)


Heterozygous FH RUTHERFORD-2 (N = 331)

CV

Outcom

esCV

Out

com

es

Jean-Baptiste Joseph Fourier1768 – 1830

Fourier demonstrated how the conduction of heat in solid bodies may be analyzed in terms of the infinite mathematical series now called by his name, “The Fourier Series.” A French mathematician, Egyptologist, and administrator, Fourier influenced mathematical physics and is also credited with the discovery of the greenhouse effect.

Andreas Vesalius1514 – 1564

Vesalius was a Flemish anatomist and physician, known as the founder of modern anatomy. He renewed the practice of human dissection and authored De humani corporis fabrica (On the Fabric of the Human Body), which revolutionalized the study of anatomy. He accurately depicted the anatomy of the human heart.

Effect of EVolocumab in PatiEntS at High CArdiovascuLar RIsk WithoUt Prior Myocardial Infarction or Stroke

A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Impact of Evolocumab on Major Cardiovascular Events in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or StrokePurposeAssess the effect of lowering LDL-C with evolocumab on major cardiovascular events in subjects without a prior MI or stroke at high risk of a cardiovascular event

*All 4 criteria needed. †May not be inclusive of all study details. ‡For adults at high cardiovascular risk without past MI or stroke and receiving optimized lipid-lowering therapy, who are randomized, regardless of discontinuation of investigational product or commencing commercial PCSK9 inhibitors.

Evolocumab is investigational for this population/use.

Key Secondary Endpoints‡ (Time to:)

• MI, ischemic stroke, or any ischemia-driven arterial revascularization

• CHD death, MI, or any ischemia-driven arterial revascularization

• CV death, MI, or stroke• MI• Any ischemia-driven arterial revascularization• CHD death• CV death• All-cause of death• Ischemic stroke

Primary Endpoints‡ (Time to:)

• CHD death, MI, or ischemic stroke, whichever occurs first

• CHD death, MI, ischemic stroke, or any ischemia-driven arterial revascularization, whichever occurs first

STUDY INFORMATION†

Key Exclusion Criteria

• MI or stroke prior to randomization

• CABG < 3 months prior to screening

• Uncontrolled HTN (sitting systolic BP > 180 mmHg or diastolic BP > 110 mmHg) at screening

• Fasting TG ≥ 500 mg/dL (5.7 mmol/L) at screening

• Last measured LVEF < 30% or NYHA Functional Class III/IV

Amgen Clinical Study: 20170625 High Cardiovascular Risk Without Prior MI or Stroke | Study Status: Active

Patients at High Cardiovascular Risk Without Prior MI or Stroke*(N ~ 13,000)

• Age ≥ 50 (men) or ≥ 55 (women) to < 80 years• LDL-C ≥ 100 mg/dL or non-HDL-C ≥ 130 mg/dL at screening,

after ≥ 4 weeks of optimized lipid-lowering therapy• Evidence of at least one of the following: significant CAD,

significant atherosclerotic cerebrovascular disease, significant PAD, or DM

• At least 1 high-risk feature: PVD, DM, LDL ≥ 130 mg/dL or non-HDL ≥ 160 mg/dL, Lp(a) > 125 mmol/L, known FH

Ran

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1:1

End

of S

tudy

Evolocumab + optimized LLT

≥ 6,500 subjects

Placebo + optimized stable LLT

≥ 6,500 subjects

PATIENT POPULATION TREATMENT ARMS

≥ 4 YEARS

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

A Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Assessing the Impact of Additional LDL-Cholesterol Reduction on Major Cardiovascular Events When Evolocumab Is Used in Combination With Statin Therapy in Patients With Clinically Evident Cardiovascular Disease

PurposeTo evaluate the effect of evolocumab, compared with placebo, when used in addition to other treatment for dyslipidemia on the risk of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization, in subjects with clinically evident cardiovascular disease.

Key Secondary Endpoints

• Time to CV death, MI, or stroke

• Time to all-cause death

• Time to CV death or first hospitalization for worsening heart failure

• Time to first fatal/nonfatal ischemic stroke or TIA

Primary Endpoints

• Time to CV death, MI, hospitalization for UA, stroke, or coronary revascularization

STUDY INFORMATION*


• NYHA class III or IV, or last known left ventricular ejection fraction < 30%

• Uncontrolled hypertension

• Uncontrolled or recurrent ventricular tachycardia

• Untreated hyperthyroidism or hypothyroidism

• Homozygous familial hypercholesterolemia

• LDL or plasma apheresis

Amgen Clinical Study: 20110118 | NCT Clinical Study: 01764633Secondary Prevention | Study Status: Completed, Open Label Extension Studies Ongoing

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TREATMENT ARMS

Assess for median of 26 months

PATIENT POPULATION

Patients With History of Clinically Evident CVD at High Risk for a Recurrent Event

(N = 27,564)• Age ≥ 40 to ≤ 85 years old• LDL-C ≥ 70 mg/dL or non-HDL-C ≥ 100 mg/dL• Triglycerides ≤ 400 mg/dL

Evolocumab SC Q2W or QM

Placebo SC Q2W or QM

*May not be inclusive of all study details.

Spec

ial P

opul

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nsSpecial PopulationsC

onsistent LDL-C

EffectCon

sist

ent L

DL-

C E

ffect

1749 – 1827

Laplace was a French mathematician, physicist and astronomer who made pivotal contributions to mathematical astronomy and statistics. He was best known for his investigations into the stability of the solar system and demonstrated the usefulness of probability for interpreting scientific data.

Gregor Mendel

Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 (MENDEL-2)

A Double-Blind Randomized, Placebo and Ezetimibe-Controlled, Multicenter Study to Evaluate Safety and Efficacy of Lipid Lowering Monotherapy With Evolocumab in Subjects With a 10-Year Framingham Risk Score of 10% or Less

PurposeTo evaluate the effect of both dosing regimens of evolocumab compared with ezetimibe and placebo on reduction of LDL-C in subjects with a 10-year Framingham risk score of 10% or less.


1822 – 1884

Mendel was an Austrian scientist, botanist and teacher. He is known as the “Father of Modern Genetics” and through his work on pea plants, discovered the fundamental laws of inheritance. He demonstrated that genes come in pairs and are inherited in distinct units, one from each parent.


• Mean change from baseline in LDL-C (weeks 10 and 12)

• Change from baseline in LDL-C (week 12)

• Percent change from baseline in non-HDL-C, ApoB, total cholesterol/HDL-C ratio, ApoB/ApoA1 ratio, lipoprotein (a), triglycerides, HDL-C, and VLDL-C

Primary Endpoints

• Mean percent change from baseline in LDL-C (weeks 10 and 12)

• Percent change from baseline in LDL-C (week 12)

STUDY INFORMATION*


• NYHA III or IV heart failure

• Uncontrolled cardiac arrhythmia


• Type 1 diabetes or poorly controlled type 2 diabetes

• Uncontrolled hypothyroidism or hyperthyroidism

• History of coronary heart disease

Amgen Clinical Study: 20110114 | NCT Clinical Study: 01763827Monotherapy | Study Status: Completed

TREATMENT ARMSPATIENT POPULATION

Patients With Hypercholesterolemia(N = 615)

• Age ≥ 18 to ≤ 80 years• LDL-C ≥ 100 mg/dL and < 190 mg/dL• Framingham risk score ≤ 10%• Triglycerides ≤ 400 mg/dL

Ezetimibe PO QD + Placebo Q2W or QM


Placebo SC Q2W or QM + Placebo PO QD

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Assess after 78 weeksAssess after 10 and 12 weeks

Pierre-Simon Laplace

LDL-C Assessment With PCSK9 MonoclonaL Antibody Inhibition Combined With Statin ThErapy-2 (LAPLACE-2)

A Double-Blind, Randomized, Placebo- and Ezetimibe-Controlled, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Evolocumab on LDL-C in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia

*Enrolled patients were first randomized to receive one of three open-label background statin treatments (rosuvastatin, atorvastatin, or simvastatin) for a 4-week lipid stabilization period. For the second randomization to evolocumab, placebo, or ezetimibe, all treatment groups continued to receive daily statin therapy. †Those receiving Ezetimibe had been randomized to Atorvastatin. ‡May not be inclusive of all study details.

Amgen Clinical Study: 20110115 | NCT Clinical Study: 01763866Combination Therapy | Study Status: Completed

PurposeTo evaluate the effect of both dosing regimens of evolocumab SC when used in combination with a statin, compared with placebo, on reduction of LDL-C in subjects with primary hypercholesterolemia and mixed dyslipidemia.


• Mean change from baseline in LDL-C (weeks 10 and 12)

• Change from baseline in LDL-C (week 12)

• Percent change from baseline in non-HDL-C, ApoB, total cholesterol/HDL-C ratio, and ApoB/ApoA1 ratio, lipoprotein (a), triglycerides, and VLDL-C

Primary Endpoints

• Mean percent change from baseline in LDL-C (weeks 10 and 12)

• Percent change from baseline in LDL-C (week 12)

STUDY INFORMATION‡


• NYHA III or IV heart failure

• Uncontrolled cardiac arrhythmia


• Type 1 diabetes or poorly controlled type 2 diabetes

• Uncontrolled hypothyroidism or hyperthyroidism

• Statin intolerance

PATIENT POPULATION

Patients With Hypercholesterolemia(N = 2,067)

• Age ≥ 18 to ≤ 80 years• LDL-C ≥ 80 mg/dL (receiving intensive statin)• Triglycerides ≤ 400 mg/dL

Ran

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ion*

TREATMENT ARMS


Placebo SC Q2W, QM or PO QD

Ezetimibe PO†

Assess after 78 weeksAssess after 10 and 12 weeks

-2 -2

Spec

ial P

opul

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nsSpecial PopulationsC

onsistent LDL-C

EffectCon

sist

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DL-

C E

ffect

Primary Endpoints• Percent change from baseline in LDL-C at week 12 and at the mean of weeks 10 and 12

Primary Endpoints• THOMAS-1: Percentage of participants with full administration of evolocumab at both weeks 2 and 4• THOMAS-2: Percentage of participants with full administration of evolocumab at both weeks 4 and 8

Study to Assess In-home Use of Evolocumab Using a Prefilled Syringe or a Prefilled Autoinjector/PenStudy to Assess in Home Use of Evolocumab Administration Using Either an Automated Mini-doser or a Prefilled Autoinjector/Pen

Purpose: • THOMAS-1: To evaluate users’ ability to administer a full dose of evolocumab in a home-use setting using either a

pre-filled syringe or autoinjector/pen.• THOMAS-2: To evaluate users’ ability to administer a full dose of evolocumab in a home-use setting using either an

automated mini-doser or autoinjector/pen.



Amgen Clinical Study: 20120348 & 20120356 NCT Clinical Study: 01849497 & 01879319Self-administration | Study Status: Completed

thomas-1

PATIENT POPULATION

Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia*

(N = 149 & 164)• Age ≥ 18 to ≤ 80 years• LDL-C > 85 mg/dL• Triglycerides ≤ 400 mg/dL

TREATMENT ARMS

Assess after 2, 4 or 8 weeks

THOMAS-1: Prefilled Syringe

THOMAS-1 & THOMAS-2: AI/pen

THOMAS-2: AMDRan

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izat

ion

Effects on Lipoprotein Metabolism From PCSK9 Inhibition Utilizing a MonoclonalAntibody

Double-blind, Randomized, Placebo-controlled, Single Site Study to Evaluate the Effects of Evolocumab Treatment, Alone and in Combination With Atorvastatin, on Lipoprotein Kinetics

Purpose: To evaluate the effect of evolocumab, atorvastatin, and combination therapy on lipoprotein kinetics.

Primary Endpoint

• Percent change from baseline in LDL-apoB-100 fractional catabolic rate at day 50

Amgen Clinical Study: 20130194 | NCT Clinical Study: 02189837Lipoprotein Kinetics | Study Status: Completed

florey



Evoolcumab SC Q2W+ Placebo PO QD

Evoolcumab SC Q2W+ Atorvastatin PO QD

Placebo SC Q2W+ Atorvastatin PO QD

Placebo SC Q2W+ Placebo PO QDPatients With Primary Hyperlipidemia and Mixed Dyslipidemia*

(N = 89)• Male, age ≥ 18 to ≤ 65 years• LDL-C ≥ 100 mg/dL and ≤ 190 mg/dL• Triglycerides ≤ 150 mg/dL• BMI between 18.0 and 32.0 kg/m2

• Framingham cardiac risk score ≤ 10%

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Assess after day 50

Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2

A Double-blind, Randomized, Multicenter Study to Evaluate Safety and Efficacy of Evolocumab, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase InhibitorPurpose: To evaluate the effect of 12 weeks of SC evolocumab Q2W and QM, compared with ezetimibe, on percent change from baseline in LDL-C in hypercholesterolemic adults unable to tolerate an effective dose of a statin.

Amgen Clinical Study: 20110116 | NCT Clinical Study: 01763905Statin Intolerance | Study Status: Completed

TREATMENT ARMS

PATIENT POPULATION

Patients With History of Intolerance to ≥ 2 Statins* (N = 307)

• Age ≥ 18 to ≤ 80 years• Not on a statin or on a low dose statin with stable

dose for ≥ 4 weeks• Subject not at LDL-C goal• Lipid lowering therapy has been stable• Triglycerides ≤ 400 mg/dL

Assess after 12 weeks

Evolocumab SC Q2W or QM and oral placebo or ezetimibe QD

Placebo SC Q2W or QM plus oral ezetimibe QDR

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-2

thomas-2

Long-TermLo

ng-T

erm

Open Label Study of Long-TERmEvaluation Against LDL-C Trial (OSLER)

A Multicenter, Controlled, Open-label Extension (OLE) Study to Assess the Long-term Safety and Efficacy of Evolocumab

Purpose: To evaluate that that long-term exposure of evolocumab will be safe and well tolerated in subjects with hypercholesterolemia.

*Standard of care as per local practice. This could include prescribed therapies and/or dietary/exercise regimens. †May not be inclusive of all study details.


• Absolute LDL-C, non-HDL-C, and ApoB at weeks 24 and 52

• Ratio of absolute total cholesterol / HDL-C at weeks 24 and 52

• Ratio of absolute ApoB / ApoA1 at weeks 24 and 52

Primary Endpoints

• Subject incidence of treatment emergent adverse events

STUDY INFORMATION†


• Experienced a treatment-related serious adverse event that led to investigational product discontinuation in the parent study

• Have an unstable medical condition, in the judgment of the investigator

• Known sensitivity to any of the products to be administered during dosing

• Currently enrolled in another investigational device or drug study (excluding evolocumab parent study), or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)

Amgen Clinical Study: 20110110 | NCT Clinical Study: 01439880Safety | Study Status: Completed


Patients With Hypercholesterolemia(N = 1,324)

• Age ≥ 18 to ≤ 75 years • Complete a qualifying evolocumab

parent study

Evolocumab + Standard of care*

Standard of care*Ran

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Assessed at 24 and 52 weeks

Evaluating PCSK9 Binding antiBody Influence oN coGnitive HeAlth in High cardiovascUlar Risk Subjects

A Double-Blind, Placebo Controlled, Multicenter Study to Assess the Effect of Evolocumab on Cognitive Function in Patients With Clinically Evident Cardiovascular Disease and Receiving Statin Background Lipid Lowering Therapy: A Study for Subjects Enrolled in the FOURIER (Study 20110118) TrialPurpose: To evaluate change over time in neurocognitive testing in patients receiving statin therapy in combination with evolocumab, compared with patients receiving statin therapy in combination with placebo.

TREATMENT ARMS

Assess at baseline, weeks 24, 48, 96, 144 and end of study visit

PATIENT POPULATION

Patients Enrolled in FOURIER Study*

(N =1,974)

Evolocumab SC Q2W or QM + background statin therapy

Placebo SC Q2W or QM + background statin therapy



Durable Effect of PCSK9 AntibodyCompARed WiTh PlacEbo Study

A Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate Long-Term Tolerability and Durable Efficacy of Evolocumab on LDL-C in Hyperlipidemic SubjectsPurpose: To evaluate the efficacy, safety, and tolerability of 52 weeks of SC evolocumab compared with placebo when added to assigned background lipid-lowering therapy.

Amgen Clinical Study: 20110109 | NCT Clinical Study: 01516879


Efficacy | Study Status: Completed

Neurocognition | Safety | Study Status: Completed

TREATMENT ARMS

Assess at 52 weeksPATIENT POPULATION

Patients With Hypercholesterolemia* (N = 905)

• Age ≥ 18 to ≤ 80 years • LDL-C ≥ 75 mg/dL and on background lipid-lowering therapy:

– LDL-C < 100 mg/dL with diagnosed CHD or CHD risk equivalent – LDL-C < 130 mg/dL without diagnosed CHD or CHD risk equivalent – OR on maximal background lipid-lowering therapy

• Triglycerides ≤ 400 mg/dL

Ran

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ion Evolocumab SC QM

+ background LLT

Placebo SC QM + background LLT

Primary Endpoint• Percent change from baseline in LDL-C at 52 weeks

Primary Endpoint• Mean change from baseline in spatial working memory strategy index of executive function Z score

Sir William Osler1849 – 1919

The “Father of Modern Medicine,” Sir William Osler was a Canadian pathologist, physician, and educator. He was the first to bring medical students out of the lecture hall for bedside clinical training and created the first residency program for specialty training. Osler was also one of the four founding professors of Johns Hopkins University Medical School.

ImagingIm

agin

g

GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound

A Randomized, Double-Blind, Multi-Center, Placebo-Controlled, Parallel-Group Study to Determine the Effects of Evolocumab Treatment on Atherosclerotic Disease Burden as Measured by Intravascular Ultrasound in Subjects Undergoing Coronary Catheterization

Purpose: To evaluate whether LDL-C lowering with evolocumab results in greater change from baseline in PAV at week 78 than placebo in adults with coronary artery disease taking lipid lowering therapy.


Amgen Clinical Study: 20120153 | NCT Clinical Study: 01813422Plaque | Study Status: Completed

TREATMENT ARMS


PATIENT POPULATION

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Patients With Evidence of Coronary Heart Disease(N = 970)

• Age ≥ 18 years to ≤ 99 years• Clinically indicated coronary angiogram• Left main coronary artery < 50% reduction in lumen

diameter• Fasting LDL-C ≥ 80 mg/dL with or without additional

risk factors, or, LDL-C ≥ 60 to < 80 mg/dL in the presence of additional risk factors

Evolocumab SC QM

Placebo SC QM

Seymour Glagov 1925 – 2008

Glagov was an American physician and pathologist who was the first to describe the atherosclerotic process and vascular remodeling. He demonstrated that as an atherosclerotic plaque began to build up within an artery, the arterial wall would compensate by expanding to maintain normal blood flow, known as the “Glagov phenomenon”.


• Change in TAV from baseline to week 78

• Percentage of patients with regression in PAV and TAV

Primary Endpoints

• Change in PAV from baseline to 78 weeks

STUDY INFORMATION*

Key Exclusion Criteria• Coronary artery bypass graft surgery < 6 weeks prior to the

qualifying IVUS • NYHA III or IV heart failure, or last known left ventricular

ejection fraction < 30%• Uncontrolled cardiac arrhythmia• Known hemorrhagic stroke• Uncontrolled hypertension• Type 1 diabetes or poorly controlled type 2 diabetes• Fasting triglycerides ≥ 400 mg/dL (4.5 mmol/L)• Moderate to severe renal dysfunction

Effects of PCSK9 Inhibition on Arterial Wall Inflammation Study in Patients With Elevated Lp(a)Purpose: To assess the effects of PCSK9 inhibition on the arterial wall inflammation in patients with elevated Lp(a).


A double-blind, placebo-controlled, multicenter, randomized study evaluating the effect of evolocumab on coronary atherosclerotic plaques as assessed by OCT in subjects with an NCSTE-ACS who are taking maximally tolerated statin therapy Purpose: To evaluate the effect of evolocumab on FCT in subjects with NSTE-ACS who are taking maximally tolerated statin therapy



Plaque | Study Status: Recruiting

Arterial wall inflammation | Study Status: Completed

Primary Endpoint• Absolute change in minimum FCT from baseline to week 50

Primary Endpoint• Effect of evolocumab on Lp(a), as measured by percentage change from baseline at week 16 in TBR of an index vessel

by FDG-PET/CT in patients with baseline Lp(a) ≥ 50 mg/dL and LDL-C ≥ 100 mg/dL

anitschkow

High-ResolUtion Assessment of CoronarY Plaques in a Global Evolocumab RaNdomized Study

Assess at 50 weeks

Patients with Coronary Artery Disease* (N = 150)

• Age ≥ 18 years • Clinical indication for coronary angiography due to NSTE-ACS • Angiographic evidence of CAD in the vessel targeted for OCT

OC

T

Evolocumab SC QM

Placebo SC QM

TREATMENT ARMS

PATIENT POPULATION

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TREATMENT ARMS

Patients With Hyperlipidemia, Dyslipidemia* (N = 129)• Age 50 to ≤ 80 years• Lp(a) ≥ 50 mg/dL • LDL-C ≥ 100 mg/dL• Lipid-lowering therapy including statin dose unchanged for at

least 8 weeks prior to screening

Evolocumab SC QM with AI Pen

Placebo SC QM with AI Pen

Assess at 16 weeks

PATIENT POPULATION

A RaNdomized Double-blInd Placebo-ConTrolled Study Characterizing THe Effects of PCSK9 Inhibition On Arterial Wall Inflammation in Patients With Elevated Lp(a)


Familial H

ypercholesterolemia (FH

)Fam

ilial

Hyp

erch

oles

tero

lem

ia (F

H)

Primary Endpoint• Percent change from baseline in LDL-C at week 12 for Part A and Part B

Trial Evaluating PCSK9 Antibody in Subjects With LDL Receptor Abnormalities (TESLA)

2-part, Phase 2/3 Study to Assess the Safety, Tolerability and Efficacy of Evolocumab in Subjects With Homozygous Familial HypercholesterolemiaPurpose: To determine the safety, tolerability, and efficacy of evolocumab in patients with homozygous familial hypercholesterolemia (HoFH).

*May not be inclusive of all study details.Part A: Open label, single arm, multi-center pilot study to evaluate safety, tolerability and efficacy of evolocumab in subjects with HoFH Part B: Double blind, randomized, placebo-controlled, multi-center study to evaluate safety, tolerability and efficacy of evolocumab in subjects with HoFH

RedUction of LDL-C With PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study-2 (RUTHERFORD-2)

A Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Evolocumab on LDL-C in Subjects With Heterozygous Familial HypercholesterolemiaPurpose: To evaluate the effect of both dosing regimens of evolocumab SC compared with placebo on reduction of LDL-C in subjects with heterozygous familial hypercholesterolemia.



Heterozygous FH | Study Status: Completed

Homozygous FH | Study Status: Completed

Primary Endpoints• Mean percent change from baseline in LDL-C (weeks 10 and 12)• Percent change from baseline in LDL-C (week 12)*May not be inclusive of all study details.

PATIENT POPULATION PATIENT POPULATION

Patients With Homozygous Familial Hypercholesterolemia*

(N = 58)• Age ≥ 12 to ≤ 80 years• LDL-C ≥ 130 mg/dL• Triglycerides ≤ 400 mg/dL

Patients With Homozygous Familial Hypercholesterolemia

(N = 58)• Age ≥ 12 to ≤ 80 years• LDL-C ≥ 130 mg/dL• Triglycerides ≤ 400 mg/dL

Evolocumab SC QM

Evolocumab SC QM

Placebo SC QMR

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TREATMENT ARM

TREATMENT ARMS

PART B (PHASE 3)PART A (PHASE 2)



Trial Assessing Efficacy, Safety and Tolerability of PCSK9 InHibition in PediAtric SUbjectS With GenEtic LDL DisordeRs (HAUSER-RCT)

Double-blind, Randomized, Multicenter, Placebo-Controlled Study to Characterize the Efficacy, Safety, and Tolerability of 24 Weeks of Evolocumab for LDL-C Reduction in Pediatric Subjects 10 to 17 Years of Age With HeFHPurpose: To assess safety and efficacy of evolocumab in paediatric subjects aged 10-17 years diagnosed with heterozygous familial hypercholesterolemia.


*May not be inclusive of all study details. †Depending on lipid apheresis status; option to change dosing regimens at week 12 or 24 based on LDL-C and serum unbound PCSK9 levels

Trial Assessing Long Term USe of PCSK9 Inhibition in Subjects WIth Genetic LDL Disorders

A Multicenter, Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of Evolocumab on LDL-C in Subjects With Severe Familial HypercholesterolemiaPurpose: To assess the long term safety and tolerability of evolocumab in adolescents and adults with severe familial hypercholesterolemia.



Heterozygous and Homozygous FH | Study Status: Completed

Pediatrics | Study Status: Recruiting

Primary Endpoint• Subject incidence of treatment emergent adverse events

Primary Endpoint• Percentage change from baseline in LDL-C levels at week 24

hauser

Patients With Heterozygous Familial Hypercholesterolemia*

(N =150)• Male or female ≥ 10 to ≤ 17 years of age• On an approved statin with stable optimized dose

for ≥ 4 weeks• Other lipid-lowering therapy stable for ≥ 4 weeks

(fibrates must be stable for ≥ 6 weeks) TREATMENT ARMS

Assess at 24 weeksPATIENT POPULATION

Evolocumab SC QM

Placebo SC QM

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PATIENT POPULATION

Patients With Heterozygous Familial Hypercholesterolemia* (N = 331)

• Age ≥ 18 to ≤ 80 years• Diagnosis of heterozygous familial hypercholesterolemia• On a stable dose of an approved statin and lipid-regulating medication• LDL-C ≥ 100 mg/dL• Triglycerides ≤ 400 mg/dL


Placebo SC Q2W or QMRan

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TREATMENT ARMS

Assess after 10 and 12 weeksPATIENT POPULATION

TREATMENT ARM

PATIENT POPULATION

Patients With Familial Hypercholesterolemia or PCSK9 Mutations* (N = 300)

• Males and females ≥ 12 to ≤ 80 years of age• Stable low-fat diet and lipid-lowering therapies for at least 4 weeks• Fasting triglycerides ≤ 400 mg/dL• Bodyweight of ≥ 40 kg at screening

Evolocumab SC Q2W or QM†

Assess after up to 5 yearsPATIENT POPULATION

-2

Special PopulationsSpecial Populations

Fam

ilial

Hyp

erch

oles

tero

lem

ia (F

H)

Evolocumab Compared to LDL-C Apheresis in Patients Receiving LDL-C Apheresis Prior to Study Enrollment

A Randomized, Actively Controlled, Open-label, Multicenter Study of Efficacy and Safety of Evolocumab Compared With Low Density Lipoprotein Cholesterol (LDL-C) Apheresis, Followed by Single-Arm Evolocumab Administration in Subjects Receiving LDL-C Apheresis Prior to Study EnrollmentPurpose: To evaluate the efficacy of subcutaneous (SC) evolocumab, compared to regularly scheduled low-density lipoprotein cholesterol (LDL-C) apheresis, on reducing the need for future apheresis.

Amgen Clinical Study: 20140316 | NCT Clinical Study: 02585895Apheresis | Study Status: Completed

Primary Endpoint• Percentage of participants with apheresis avoidance at the end of randomized therapy

delaval


Primary Endpoint• Number of participants with treatment related adverse events (week 12)

Assess at 12 weeks

Patients With HoFH*(N = 30)

• Age ≥ 12 to ≤ 80 years • Diagnosis of HoFH based on LDL-C, familial

history and xanthoma • On lipid-lowering therapy stable for 4 weeks

Evolocumab SC QM + background LLT

PATIENT POPULATION

TREATMENT ARM


Evaluation of Evolocumab Efficacy in Diabetic Adults With Hypercholesterolemia/Mixed Dyslipidemia

A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Evolocumab on LDL-C in Subjects With Type 2 Diabetes Mellitus and Hypercholesterolemia/Mixed DyslipidemiaPurpose: To evaluate the effect of 12 weeks of subcutaneous evolocumab taken monthly compared with subcutaneous placebo taken monthly on low density lipoprotein cholesterol (LDL-C) in adults with type 2 diabetes mellitus and high blood cholesterol on a maximally tolerated oral dose of statin of at least moderate-intensity.


Primary Endpoints• Percent change from baseline in LDL-C at the mean of weeks 10 and 12 • Percent change from baseline in LDL-C at week 12

banting

Diabetes | Study Status: Completed


Patients With Hypercholesterolemia*

(N = 39)• Age ≥ 18 years• Pre-apheresis LDL-C is

≥ 100 mg/dL• Triglycerides ≤ 400 mg/dL

Evolocumab SC Q2W

LDL-C Apheresis QW or Q2W

Evolocumab SC Q2W

Ran

dom

izat

ion

PATIENT POPULATION TREATMENT ARMS

Assess after 6 weeks Assess up to 24 weeks


Assess at 12 weeks

TREATMENT ARMS

Patients With Hypercholesterolemia, Mixed Dyslipidemia, Type 2 Diabetes*

(N = 424)• Age ≥ 18 years• Hemoglobin A1c < 10%• Triglycerides ≤ 600 mg/dL

Evolocumab SC QM

Placebo SC QM

Ran

dom

izat

ion

Safety and Efficacy of Evolocumab in Combination With Statin Therapy in Adults With Diabetes and Hyperlipidemia or Mixed Dyslipidemia

A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety and Efficacy of Evolocumab in Combination With Statin Therapy in Diabetic Subjects With Hyperlipidemia or Mixed Dyslipidemia

Safety and ToleRAbility of EvolocuMab in IndiAN Subjects with Homozygous Familial Hypercholesterolemia

Purpose: To describe the safety and tolerability of evolocumab in subjects with homozygous familial hypercholesterolemia (HoFH) in India.

Amgen Clinical Study: 20170199 | NCT Clinical Study: 03403374Homozygous FH | Study Status: Recruiting

ramanA Multicenter, Open-label, Single-arm, Study to Evaluate Safety and Tolerability of Evolocumab in Patients with Homozygous Familial Hypercholesterolemia (HOFH) in India

Purpose: To evaluate the effect of 12 weeks of subcutaneous evolocumab in combination with statin therapy (atorvastatin) on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in diabetic adults with hyperlipidemia or mixed dyslipidemia.

Amgen Clinical Study: 20120119 | NCT Clinical Study: 02662569Diabetes | Study Status: Completed

Primary Endpoints• Percent change from baseline in LDL-C at the mean of weeks 10 and 12 • Percent change from baseline in LDL-C at week 12

berson

Evolocumab SC Q2W + Atorvastatin PO QDPatients With Hypercholesterolemia, Mixed Dyslipidemia, Type 2 Diabetes*

(N = 986)• Age ≥ 18 years to ≤ 80 years• Males and females with type 2 diabetes• Lipid-lowering therapy unchanged for ≥ 4 weeks

Placebo SC Q2W + Atorvastatin PO QD

Evolocumab SC QM + Atorvastatin PO QD

Placebo SC QM + Atorvastatin PO QDRan

dom

izat

ion

TREATMENT ARMSAssess at 12 weeks

PATIENT POPULATION

PATIENT POPULATION

Spec

ial P

opul

atio

nsSp

ecia

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Safety, Tolerability & Efficacy on LCL-C of Evolocumab in Subjects With HIV and Hyperlipidemia/Mixed Dyslipidemia

A Double Blind, Randomized, Placebo Controlled, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy on LDL-C of Evolocumab in Subjects With HIV and Hyperlipidemia and/or Mixed DyslipidemiaPurpose: To evaluate if evolocumab SC QM will be well tolerated and result in greater reduction of LDL-C, defined as percentage change from baseline at week 24, compared with placebo QM in HIV-positive subjects with hyperlipidemia and/or mixed dyslipidemia.

Amgen Clinical Study: 20130286 | NCT Clinical Study: 02833844HIV | Study Status: Active, Not Recruiting

Primary Endpoint• Percentage change from baseline in LDL-C at week 24

beijerinck



Assess at 24 weeks Assess at 24 weeks

Patients With Hyperlipidemia, Dyslipidemia and HIV Infection*

(N = 467)• Age ≥ 18 years• HIV viral load ≤ 50 copies/mL at screening and

≤ 200 copies/mL for ≥ 6 months• On a stable dose of optimized lipid lowering therapy for ≥ 4 wks• Fasting triglycerides ≤ 600 mg/dL

EvolocumabSC QM

PlaceboSC QM

EvolocumabSC QM

Ran

dom

izat

ion

PART 2PART 1

AI = auto injector; AI/pen = autoinjector/pen; AIDS = acquired immune deficiency syndrome; AMD = automated minidoser; ApoA1 = apolipoprotein A1; ApoB = apolipoprotein B; BMI = body mass index; BP = blood pressure; CABG = coronary artery bypass graft; CAD = coronary artery disease; CD4 = cluster of differentiation 4; CHD = coronary heart disease; CV = cardiovascular; D = day; DM = diabetes mellitus; FCT = fibrous cap thickness; FDG-PET/CT = fluorodeoxyglucose positron emission tomography/computed tomography; HDL-C = high density lipoprotein cholesterol; HeFH = heterozygous familial hypercholesterolemia; HIV = human immunodeficiency virus; HMG-CoA = 5-hydroxy-3-methylglutaryl-coenzyme A; HMG-CoAR = 3-hydroxyl-3-methylglutaryl-coenzyme A reductase; HoFH = homozygous familial hypercholesterolemia; HTN = hypertension; IDL = intermediate-density lipoprotein; IVUS = intravascular ultrasound; LDL = low-density lipoprotein; LDL-C = low-density lipoprotein cholesterol; LLT = lipid lowering therapy; Lp(a) = lipoprotein (a); LVEF = left ventricular ejection fraction; mAb = monoclonal antibody; MI = myocardial infarction; NSTE-ACS = non-ST-elevation acute coronary syndrome; NYHA = New York Heart Association; OCT = optical coherence tomography; OLE = open label extension; PAD = peripheral arterial disease; PAV = percent atheroma volume; PCSK9 = proprotein convertase subtilisin/kexin type 9; PFS = prefilled syringe; PO = orally; PVD = polyvascular disease; Q2W = once every 2 weeks; Q4W = once every 4 weeks; QD = once daily; QM = once monthly; QW = once weekly; SC = subcutaneous; TAV = total atheroma volume; TBR = target-to-background ratio; TG = triglycerides; TIA = transient ischemic attack; TSH = thyroid stimulating hormone; UA = unstable angina; ULN = upper limit of normal; VLDL = very-low density lipoprotein; VLDL-C = very low-density lipoprotein cholesterol.

Reference: www.clinicaltrials.gov

Evolocumab PROFICIO Program

PROFICIO REAL WORLD EVIDENCE

Real World Evidence Generation

PROFICIO is Amgen’s program of clinical and real-world evidence studies investigating the impact of evolocumab and use of lipid-lowering therapies across multiple patient populations. PROFICIO includes large scale prospective real-world studies. These studies play an important role in understanding the real-world use of lipid-lowering therapies and their impact on cardiovascular disease outcomes.

Investigational program for evolocumab.

PROFICIO GALLERY OF REAL-WORLD EVIDENCEProgram to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations

United States and C

anada

CardioVascular MultidimensionalOBservational Investigation of the Use of PCSK9 Inhibitors

A North American Registry of Patients With ASCVD Aimed at UnderstandingPatterns of Care in ASCVD While Evaluating the Real World Effectiveness of PCSK9inhibitors

Amgen Observational Study: 20180059 | NCT Clinical Study: 04197453ASCVD | Study Status: Active

August Ferdinand Möbius1790 – 1868

Möbius was a German mathematician and astronomer who is best known for his discovery of the Möbius strip. Möbius was also the first to introduce homogeneous coordinates into analytic geometry, the extension of coordinates to include a point at infinity. Many mathematical concepts are named after him, including the Möbius plane, the Möbius transformations, and the Möbius transform of number theory.

PurposeA North American registry of patients with ASCVD aimed at understanding patterns of care in ASCVD while evaluating the real world effectiveness of PCSK9 inhibitors (PCSK9i) to reduce cardiovascular events.

heymans

zerbini

shennong 神农

EUROPE

CANADA, COLOMBIA, KUWAIT, MEXICO, AND SAUDI ARABIA

CHINA

UNITED STATES

UNITED STATES AND CANADA

gould

cvMobius

Reference: www.clinicaltrials.gov.Investigational program for evolocumab.

cvMobius

Key Secondary Outcomes

• To understand the strengthsand limitations of dataharvested directly fromEHR systems as comparedwith prospectively collectedinformation

Primary Outcomes

• Composite of all-causemortality, non-fatal MI,non-fatal IS

STUDY INFORMATION

Key Exclusion Criteria (Consented Arm)*

• ESRD or stage 5 CKD

• Anticipated life expectancy less than6 months

• On a PCSK9i prior to their index event†

Key Exclusion Criteria (EHR Arm)*

• No exclusion criteria will be applied for the EHR arm

*Not inclusive of all criteria. †Subjects with prior PCSK9i use occurring and ending before the 12-month period prior to enrollment and before the index ASCVD event will be considered for inclusion.

PATIENT POPULATION* PATIENT POPULATION*

Annual Data Extractions for

5 Years

4.5–5 Years

Patients With a Recent ASCVD Event or Revascularization Procedure

(N = 8,500)• With LDL-C ≥ 70 on current

therapy or• Who have recently initiated a

PCSK9i• Planned follow-up within the

health system

Patients With Evidence of Clinical ASCVD (40 health systems,

N = all eligible subjects) Captured in the

Inpatient or Outpatient Care Setting

Follow-up Period:

Data Collection

Through EHR

Follow-up Period:

Data Collection

Through eCRF

CONSENTED ARM EHR ARM

https://clinicaltrials.gov/ct2/show/NCT04197453?term=NCT04197453&draw=2&rank=1

EuropeU

nite

d St

ates

Corneille Jean François Heymans 1892 – 1968

Heymans was a Belgian physiologist who was awarded the Nobel Prize in 1938 for showing how blood pressure and oxygen content of the blood are measured by the body and transmitted to the brain. Experimenting with anesthetized dogs, Heymans demonstrated the existence of a set of sensory organs, known pressoreceptors and chemoreceptors. He was the Editor-in-Chief of Archives Internationales de Pharmacodynamie et de Thérepie for many years.

CHaractEristics of HYperlipidaeMic PAtieNts at Initiation of Evolocumab and Treatment PatternS

An Observational Serial Chart Review of Evolocumab Use in European Subjects With Hyperlipidaemia

PurposeReview of clinical characteristics of patients who are prescribed evolocumab and how their treatment is managed.

*BMI, smoking status, chronic kidney disease, history of hypertension, vascular bed involvement. †Up to 26 weeks prior to and up to 52 weeks post first dose of evolocumab.


• TC, LDL-C, HDL-C, non-HDL-C, TG values duringobservation period†

• Evolocumab dose in mg• Lipid-modifying therapies

over time, type, dose, anddose frequency during theobservation period

Primary Outcomes

• Age at initiation ofevolocumab

• FH status

• Diabetic status

• CV history

• CV risk factors*

• History of statinintolerance

STUDY INFORMATION

Exclusion Criteria

• Enrolled in an interventional study of PCSK9inhibitor within 12 weeks prior to initiation ofevolocumab

• Received commercially available PCSK9 inhibitorwithin 12 weeks prior to initiation of evolocumab

Amgen Observational Study: 20130296 | NCT Clinical Study: 02770131Hypercholesterolaemia | Study Status: Active

Patients With Hyperlipidaemia Who Have Received Evolocumab

as Part of Routine Clinical Management(N ≤ 2,000)

• Adults ≥ 18 years of age• Initiated on evolocumab after

August 1, 2015• Received at least one dose of

evolocumab

Follow-up Period: Data Collection

Baseline Period: Relevant Baseline Data Collection

PATIENT POPULATION

30 Months Post-initiation of Evolocumab

Up to 26 Weeks Prior to Initiation of Evolocumab

Data Collection

heymans

Index Date: 1st Dose of

Evolocumab

Getting to an ImprOved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management: A Registry of High Cardiovascular Risk Subjects in the United States

A Prospective Multicenter Observational Cohort Study of ASCVD Subjects Designed to Describe Practice Patterns of Cholesterol Management in the US

Amgen Observational Study: 20150230 | NCT Clinical Study: 02993120ASCVD and Elevated LDL-C | Study Status: Active

gould

Benjamin Apthorp Gould1824 – 1896

Gould was an American astronomer who is most noted for creating the Astronomical Journal star catalogs that helped describe the list of constellations of the Southern Hemisphere. He is also known for founding of the Argentine National Observatory and the Argentine National Weather Service.

PurposeTo better understand cholesterol treatment patterns in the context of a changing landscape in subjects with ASCVD.

Secondary Outcomes

• LDL-C levels and measurementpatterns

• Subject characteristics• Subject understanding of CV

risk• Goals of lipid management• Attitudes toward LLT

Primary Outcomes

• LDL-C treatmentpatterns

STUDY INFORMATION

Exclusion Criteria†

• Unable or unwilling to provide informed consentincluding but not limited to cognitive or languagebarriers

• Current or planned participation in aninterventional clinical study involving anyinvestigational medical device or drug treatment atthe time of enrollment or in the 6 months prior toenrollment

• Life expectancy < 12 months

PROSPECTIVE DATA COLLECTIONPATIENT POPULATION†

Patients With ASCVD and Elevated LDL-C

(N = 5,006)• Established ASCVD* with

LDL-C ≥ 70 mg/dL or currentlyon a PCSK9i

Cohort 1: Subjects takinga PCSK9i at baseline (n = 554)

Cohort 2: Subjects withLDL-C ≥ 100 mg/dL (n = 1,802)

Cohort 3: Subjects withLDL-C 70–99 mg/dL (n = 2,650)

Assess at 6 Month Intervals for 24 Months

*Defined as meeting ≥ 1 of the following criteria: CAD; prior history of MI; coronary or other arterial revascularization; ischemic stroke or TIA; documented PAD secondary to atherosclerosis; carotid artery stenosis; LDL-C ≥ 70 mg/dL (except in subjects assigned to the PCSK9i cohort). †Not inclusive of all criteria.

Up to 12 Months

Retrospective Chart Review at

Enrollment

Reference: www.clinicaltrials.gov and Data on file, Amgen; 2020.Investigational program for evolocumab. Reference: www.clinicaltrials.gov

and Cannon CP, et al. Am Heart J. 2020; 219(0):70-77.

https://clinicaltrials.gov/ct2/show/NCT02993120?term=02993120&draw=2&rank=1

https://clinicaltrials.gov/ct2/show/NCT02770131?term=02770131&draw=2&rank=1

China

Can

ada

| C

olom

bia

| K

uwai

t |

Mex

ico

| S

audi

Ara

bia

MultiZonal ObsERvational Study Conducted By ClinIcal Practitioners on Evolocumab Use iN Subjects With HyperlipIdemia

An Observational Chart Review of Subjects Receiving Evolocumab as Part of Routine Clinical Management of Hyperlipidemia in Canada and Selected Countries in Latin America and the Middle East

Amgen Observational Study: 20160327Hyperlipidemia | Study Status: Active

zerbini

Euryclides de Jesus Zerbini 1912 – 1993

Zerbini was a Brazilian physician and cardiac surgeon who is internationally known for performing the first heart transplantation in Latin American in 1968. He is also credited for creating the famous and respected clinical and research center Instituto do Coração da Universidade de São Paulo (Heart Institute of the University of São Paulo), in São Paulo, Brazil. “Omnia vincit labor” (nothing surpasses work) was Zerbini’s most repeated teaching to motivate his students.

PurposeDescribe the clinical characteristics of subjects prior to initiation of evolocumab, LDL-C concentrations, and treatment patterns of evolocumab and other lipid modifying therapies over 12 months of follow-up after evolocumab initiation.


• LDL-C and other cholesterol levels • Use of evolocumab at treatment initiation and

over 12 months of follow-up• LMT at treatment initiation and over 12 months

of follow-up

Primary Outcomes

• Clinical characteristics prior to initiation of evolocumab as assessed in relation to:

– FH status

– Diabetic status

– CV History

– LDL-C

STUDY INFORMATION

Exclusion Criteria

• Use of any PCSK9i within 6 months prior to initiation of evolocumab

PATIENT POPULATION

1 Year Post-initiation of evolocumab

Up to 6 Months Prior to Initiation of evolocumab

Data Collection

Patients With Hyperlipidemia(N ~ 750)

• Adult subjects ≥ 18 years of age

• Initiated on evolocumab after August 1, 2017

• Received at least one dose of evolocumab before enrollment and ≤ 6 months exposure


Baseline Period: Statin/LMT/LDL-C

Data Collection

Index Date: 1st Dose of

Evolocumab

Effectiveness of Evolocumab Used in Combination With Standard of Care at Long-term in Chinese Patients With Established Atherosclerotic Cardiovascular Disease

A Comparative Study to Evaluate the Effect of Treatment With Evolocumab in Combination With SOC, Compared With SOC Alone, on the Risk for Major Cardiovascular Events in Chinese Patients with Established ASCVD

Amgen Observational Study: 20180442ASCVD | Study Status: Active

shennong 神农

PurposeTo evaluate the effect of treatment with evolocumab in combination with SOC, compared with SOC alone, on the risk for CV death, MI, stroke, hospitalization for UA, or coronary revascularization, whichever occurs first, in patients with established ASCVD.

*Not inclusive of all key exclusion criteria.


• Baseline characteristics (i.e. demographics, medical history, prior and concurrent LLT)

• Time to CV death, MI, or stroke, whichever occurs first

• Change and percentage change in LDL-C from baseline to follow-up

• AEs and ADRs

Primary Outcomes

• Time to CV death, MI, hospitalization for unstable angina, stroke, or coronary revascularization, whichever occurs first

STUDY INFORMATION

Key Exclusion Criteria*

• Stroke within the past month

• Past hemorrhagic stroke

• Stroke due to thromboembolic event (i.e. atrial fibrillation, patient without appropriate anticoagulation)

• NYHA Class III or IV or last known LVEF < 30%

• Any prior use of any PCSK9 inhibitor

PATIENT POPULATION TREATMENT PERIOD

Assess Every 6 Months For Up to 6 Years

Assess at 3, 6 and 12 Months

Chinese Patients With Established ASCVD(N = 7,000)

• Adults ≥ 18 years of age • Symptomatic PAD, or past MI or ischemic

stroke PLUS event in the past 2 years OR multiple prior events OR multivessel coronary disease, OR type 2 diabetes

• Fasting LDL-C ≥ 70 mg/dL or non-HDL-C ≥ 100 mg/dL

• Fasting TG ≤ 400 mg/dL


SOC AloneN = 3,500

SOC + EvolocumabN = 3,500

Shennong~3000 B.C

Shennong, venerated as the father of Chinese medicine, is said to have tasted hundreds of herbs to test their medical value. The most well-known work attributed to Shennong is the Shennong Bencao Jing (Herbal Classic of Shennong). This work lists the various medicinal herbs that were discovered by Shennong. As a result of his efforts, numerous herbs became routinely used for health care, and the knowledge was handed down by oral tradition for centuries.

Reference: Data on file, Amgen; 2020.Investigational program for evolocumab. Reference: Data on file, Amgen; 2020.

USA-145-82060

ADR = adverse drug reactions; AE = adverse event; ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; CAD = coronary artery disease; CKD = chronic kidney disease; CV = cardiovascular; eCRF = electronic case report form; EHR = electronic health record; ESRD = end stage renal disease; FH = familial hypercholesterolaemia; HDL-C = high density lipoprotein-cholesterol; LDL-C = low density lipoprotein-cholesterol; LLT = lipid-lowering treatment; LMT = lipid-modifying therapy; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NYHA = New York Heart Association; PAD = peripheral arterial disease; PCSK9 = proprotein convertase subtilisin/kexin type 9; PCSK9i = proprotein convertase subtilisin/kexin type 9 inhibitor; SOC = standard of care; TC = total cholesterol; TG = triglycerides; TIA = transient ischemic attack; UA = unstable angina; US = United States.

Documents

PROFICIO...CV Outcomes CV Outcomes Jean-Baptiste Joseph Fourier 1768 – 1830 Fourier demonstrated how the conduction of heat in solid bodies may be analyzed in terms of the infinite