Evolocumab

Identification

Name
Evolocumab
Accession Number
DB09303
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.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Db09303
Protein Chemical Formula
C6242H9648N1668O1996S56
Protein Average Weight
141800.0 Da
Sequences
Not Available
Synonyms
Not Available
External IDs
  • AMG-145

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
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
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.

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.

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
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.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab 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.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Evolocumab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Evolocumab is combined with Antilymphocyte immunoglobulin (horse).
Antithymocyte immunoglobulin (rabbit)The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Evolocumab.
Asfotase alfaThe risk or severity of adverse effects can be increased when Asfotase alfa is combined with Evolocumab.
AtezolizumabThe risk or severity of adverse effects can be increased when Evolocumab is combined with Atezolizumab.
AtoltivimabThe risk or severity of adverse effects can be increased when Evolocumab is combined with Atoltivimab.
Additional Data Available
  • Extended Description
    Extended Description
    Available for Purchase

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity
    Available for Purchase

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

    Learn more
  • Evidence Level
    Evidence Level
    Available for Purchase

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

    Learn more
  • Action
    Action
    Available for Purchase

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

    Learn more
Food Interactions
Not Available

Products

Purchasing individual compounds or compound libraries for your research?
Learn More
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RepathaKit420 mg/3.5mLSubcutaneousAmgen USA Inc.2018-10-09Not applicableUS flag
RepathaKit420 mg/3.5mLSubcutaneousAMGEN INC2016-08-01Not applicableUS flag
RepathaInjection, solution140 mgSubcutaneousAmgen Europe B.V.2015-07-17Not applicableEU flag
RepathaInjection, solution140 mgSubcutaneousAmgen Europe B.V.2015-07-17Not applicableEU flag
RepathaInjection, solution140 mg/1mLSubcutaneousAmgen USA Inc.2018-10-09Not applicableUS flag
RepathaInjection, solution140 mg/1mLSubcutaneousAMGEN INC2015-08-31Not applicableUS flag
RepathaSolution120 mgSubcutaneousAmgen2017-04-04Not applicableCanada flag
RepathaInjection, solution140 mgSubcutaneousAmgen Europe B.V.2015-07-17Not applicableEU flag
RepathaSolution140 mgSubcutaneousAmgen2015-09-28Not applicableCanada flag
RepathaInjection, solution140 mgSubcutaneousAmgen Europe B.V.2015-07-17Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

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

    Learn more
  • Product Code
    Product Code
    Available for Purchase

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

    Learn more

Categories

ATC Codes
C10AX13 — Evolocumab
Drug Categories
Chemical TaxonomyProvided by Classyfire
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

Chemical Identifiers

UNII
LKC0U3A8NJ
CAS number
1256937-27-5

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]
KEGG Drug
D10557
PubChem Substance
347910432
RxNav
1665684
ChEMBL
CHEMBL2364655
Drugs.com
Drugs.com Drug Page
Wikipedia
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
4CompletedTreatmentHomozygous Familial Hypercholesterolemia HoFH1
4CompletedTreatmentType2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentChronic Kidney Disease (CKD) / High Cholesterol1
4Not Yet RecruitingTreatmentFamilial Dysbetalipoproteinemia / Hyperlipoproteinemia Type III1
4Not Yet RecruitingTreatmentHyperlipidemias1
4Not Yet RecruitingTreatmentStroke, Ischemic1
4RecruitingDiagnosticDyslipidemia Associated With Type II Diabetes Mellitus / Hypertension Arterial / Type 2 Diabetes Mellitus1
4RecruitingPreventionAtherosclerosis / Coronary Artery Bypass Grafting (CABG) / Vein Occlusion1
4RecruitingSupportive CareAtherosclerotic Vascular Diseases / Microvascular Dysfunction / Type2 Diabetes1
4RecruitingTreatmentAcute Coronary Syndromes (ACS) / Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionCutaneous; Parenteral140 MG
Injection, solutionCutaneous; Parenteral420 MG
Injection, solutionSubcutaneous140 mg/1mL
Injection, solutionSubcutaneous140 mg
KitSubcutaneous420 mg/3.5mL
SolutionSubcutaneous120 mg
Injection, solutionSubcutaneous140 mg/ml
InjectionSubcutaneous140 mg/ml
SolutionSubcutaneous140 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
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 November 25, 2020 15:47

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates