Identification

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Name
Evolocumab
Accession Number
DB09303
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Evolocumab is a monoclonal antibody designed for the treatment of hyperlipidemia by Amgen. It is a subcutaneous injection approved by the FDA for individuals on maximum statin therapy who still require additional LDL-cholesterol lowering. It is approved for both homozygous and heterozygous familial cholesterolemia as an adjunct to other first-line therapies. Evolocumab is a human IgG2 monoclonal antibody that targets the proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that targets LDL receptors for degradation, therefore reducing the liver's ability to remove LDL-cholesterol (LDL-C), or "bad" cholesterol, from the blood. Evolocumab is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface, resulting in more LDL receptors on the surface of the liver to remove LDL-C from the blood. Evolocumab is the second PCSK9 inhibitor on the market, first being alirocumab.

Protein structure
Db09303
Protein chemical formula
C6242H9648N1668O1996S56
Protein average weight
141800.0 Da
Sequences
Not Available
Synonyms
Not Available
External IDs
AMG-145
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RepathaInjection, solution140 mgSubcutaneousAmgen Europe B.V.2015-07-17Not applicableEu
RepathaKit420 mg/3.5mLSubcutaneousAmgen USA Inc.2018-10-09Not applicableUs
RepathaInjection, solution140 mgSubcutaneousAmgen Europe B.V.2015-07-17Not applicableEu
RepathaSolution120 mgSubcutaneousAmgen2017-04-04Not applicableCanada
RepathaSolution140 mgSubcutaneousAmgen2015-09-28Not applicableCanada
RepathaInjection, solution140 mg/1mLSubcutaneousAmgen USA Inc.2018-10-09Not applicableUs
RepathaInjection, solution140 mgSubcutaneousAmgen Europe B.V.2015-07-17Not applicableEu
RepathaKit420 mg/3.5mLSubcutaneousAMGEN INC2016-08-01Not applicableUs
RepathaInjection, solution140 mg/1mLSubcutaneousAmgen USA Inc.2018-10-09Not applicableUs
RepathaInjection, solution140 mgSubcutaneousAmgen Europe B.V.2015-07-17Not applicableEu
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
LKC0U3A8NJ
CAS number
1256937-27-5

Pharmacology

Indication

For the treatment of heterozygous/homozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease in patients on maximum tolerated statin therapy requiring additional LDL-cholesterol lowering.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Evolocumab is a human IgG monoclonal antibody which targets PCSK9 (proprotein convertase subtilisin/kexin type 9). PCSK9 is a serine protease produced by the liver which binds LDL receptors and creates a complex to be targeted for lysosomal degradation. LDL receptors typically bind LDL-cholesterol ("bad" cholesterol) for cellular reuptake, therefore the formation of these complexes with PCSK9 inhibits LDL receptor recycling to the cell surface, resulting in decreased cellular reuptake of LDL-C and increased levels of free LDL-C in the plasma. Individuals with familial hypercholesterolemia often may have "gain of function" mutations in the PCSK9 molecules in their body, resulting in increased LDL-C plasma levels and a consequent cardiovascular risk. Evolocumab is able to bind both the normal PCSK9 and the "gain of function" mutant, D374Y. The exact mechanism of the binding has not been published, however the precursor molecule, mAb1, is indicative of the interaction. The mAb1 molecule binds on the catalytic site of PCSK9 next to the binding site for the LDL receptor and creates hydrogen bonds and hydrophobic interactions, resulting in the steric inhibition of binding between PCSK9 and the LDL receptor. Because the formation of complexes between LDL receptor and PCSK9 are prevented, the internalized LDL receptors are less likely to be degrated by lysosomes and may recycle to the surface of the cell to serve their function of removing LDL from the blood.

Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Total bioavailability from subcutaneous injection was 82% in cynomolgus monkeys.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance

Evolocumab showed non-linear, dose-dependent clearance in healthy volunteers; clearance decreased with increasing dose.

Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Evolocumab.
AbituzumabThe risk or severity of adverse effects can be increased when Evolocumab is combined with Abituzumab.
AbrilumabThe risk or severity of adverse effects can be increased when Evolocumab is combined with Abrilumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Evolocumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Evolocumab.
AducanumabThe risk or severity of adverse effects can be increased when Evolocumab is combined with Aducanumab.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Evolocumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Evolocumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Evolocumab.
AmatuximabThe risk or severity of adverse effects can be increased when Evolocumab is combined with Amatuximab.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
  1. Authors unspecified: Evolocumab (Repatha)--a second PCSK9 inhibitor to lower LDL-Cholesterol. Med Lett Drugs Ther. 2015 Oct 12;57(1479):140-1. [PubMed:26445204]
  2. Page MM, Watts GF: Evolocumab in the treatment of dyslipidemia: pre-clinical and clinical pharmacology. Expert Opin Drug Metab Toxicol. 2015;11(9):1505-15. doi: 10.1517/17425255.2015.1073712. [PubMed:26293511]
External Links
KEGG Drug
D10557
PubChem Substance
347910432
ChEMBL
CHEMBL2364655
Drugs.com
Drugs.com Drug Page
Wikipedia
Evolocumab
ATC Codes
C10AX13 — Evolocumab
AHFS Codes
  • 24:06.24 — Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Inhibitors
FDA label
Download (1.18 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingPreventionDyslipidemia Associated With Type II Diabetes Mellitus / Percutaneous Coronary Intervention / Type 2 Diabetes Mellitus1
1CompletedTreatmentHyperlipidemias1
1CompletedTreatmentHyperlipidemias / Mixed hypercholesterolemia1
2Active Not RecruitingTreatmentAtherosclerotic Cardiovascular Diseases / Dyslipidemia (Fredrickson Type Ⅱa) / Symptomatic Atherosclerosis / Type2 Diabetes1
2CompletedTreatmentDyslipidemia (Fredrickson Type Ⅱa)1
2CompletedTreatmentHigh Cholesterol2
2CompletedTreatmentHypercholesterolemia and High Risk for Cardiovascular Events1
2CompletedTreatmentHyperlipidemias3
2RecruitingTreatmentAcute Coronary Syndromes (ACS)1
2RecruitingTreatmentCardiac Transplant1
2RecruitingTreatmentCoronary Artery Disease / Human Immunodeficiency Virus (HIV)1
2RecruitingTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF) / Heart Failure With Reduced Ejection Fraction (HFrEF) of Ischemic Etiology1
2RecruitingTreatmentSepsis1
2, 3CompletedTreatmentHomozygous Familial Hypercholesterolemia1
2, 3CompletedTreatmentSevere Familial Hypercholesterolemia1
3Active Not RecruitingTreatmentDyslipidemias2
3Active Not RecruitingTreatmentHeterozygous Familial Hypercholesterolemia1
3Active Not RecruitingTreatmentSubjects With Hyperlipidemia, Dyslipidemia and HIV Infection1
3CompletedOtherDyslipidemias1
3CompletedTreatmentAcute Coronary Syndromes (ACS)1
3CompletedTreatmentDiabetes, Hyperlipidemia, Mixed Dyslipidemia1
3CompletedTreatmentDyslipidemia (Fredrickson Type Ⅱa) / Mixed hypercholesterolemia2
3CompletedTreatmentDyslipidemias1
3CompletedTreatmentHigh Cholesterol6
3CompletedTreatmentHigh Cholesterol / Mixed hypercholesterolemia / Type 2 Diabetes Mellitus1
3CompletedTreatmentHyperlipidemia and Mixed Dyslipidemia1
3CompletedTreatmentHyperlipidemia or Mixed Dyslipidemia at High Risk for Cardiovascular Events1
3CompletedTreatmentHyperlipidemias5
3CompletedTreatmentPrimary Hyperlipidemia and Mixed Dyslipidemia1
3CompletedTreatmentSubjects With Hyperlipidemia, Dyslipidemia1
3Not Yet RecruitingPreventionCardiac Allograft Vasculopathy1
3Not Yet RecruitingTreatmentHomozygous Familial Hypercholesterolemia1
3RecruitingTreatmentCardiovascular Disease (CVD) / Hyperlipidemias1
3RecruitingTreatmentCoronary Artery Disease1
3RecruitingTreatmentCoronary Heart Disease (CHD)1
3RecruitingTreatmentDyslipidemia (Fredrickson Type Ⅱa)1
3RecruitingTreatmentDyslipidemia (Fredrickson Type Ⅱa) / Mixed hypercholesterolemia1
4Active Not RecruitingTreatmentHomozygous Familial Hypercholesterolemia HoFH1
4CompletedTreatmentType2 Diabetes Mellitus1
4Not Yet RecruitingSupportive CareCoronary Artery Disease / Microvascular Dysfunction / Type2 Diabetes1
4Not Yet RecruitingTreatmentAtherosclerosis / Coronary Artery Disease / Hyperlipidemias1
4Not Yet RecruitingTreatmentAtherosclerotic Cardiovascular Diseases1
4Not Yet RecruitingTreatmentCarotid Artery Stenosis1
4Not Yet RecruitingTreatmentCoronary Artery Disease1
4Not Yet RecruitingTreatmentFamilial Dysbetalipoproteinemia / Hyperlipoproteinemia Type III1
4RecruitingNot AvailableLipid Lowering, Vascular Inflammation1
4RecruitingDiagnosticDyslipidemia Associated With Type II Diabetes Mellitus / Hypertension Arterial / Type 2 Diabetes Mellitus1
4RecruitingPreventionAtherosclerosis / Coronary Artery Bypass Graft Surgery Patients / Vein Occlusion1
4RecruitingPreventionDyslipidemia (Fredrickson Type Ⅱa)1
4RecruitingTreatmentAtherosclerotic Cardiovascular Diseases1
Not AvailableNot Yet RecruitingDiagnosticDyslipidemia (Fredrickson Type Ⅱa) / High Cholesterol1
Not AvailableRecruitingNot AvailableDyslipoproteinemias1
Not AvailableRecruitingNot AvailableHypercholesterolemia; ASCVD; Pregnancy / Hypercholesterolemia; Pregnancy1
Not AvailableRecruitingNot AvailablePeripheral Arterial Disease (PAD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous140 mg
Injection, solutionSubcutaneous140 mg/1mL
KitSubcutaneous420 mg/3.5mL
SolutionSubcutaneous120 mg
SolutionSubcutaneous140 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Very-low-density lipoprotein particle receptor binding
Specific Function
Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein recepto...
Gene Name
PCSK9
Uniprot ID
Q8NBP7
Uniprot Name
Proprotein convertase subtilisin/kexin type 9
Molecular Weight
74285.545 Da
References
  1. Page MM, Watts GF: Evolocumab in the treatment of dyslipidemia: pre-clinical and clinical pharmacology. Expert Opin Drug Metab Toxicol. 2015;11(9):1505-15. doi: 10.1517/17425255.2015.1073712. [PubMed:26293511]

Drug created on November 11, 2015 14:05 / Updated on September 15, 2019 08:16