Alirocumab

Identification

Summary

Alirocumab is a PCSK9 inhibitor used as an adjunct to manage heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease in patients who require additional lowering of LDL-cholesterol (LDL-C).

Brand Names
Praluent
Generic Name
Alirocumab
DrugBank Accession Number
DB09302
Background

Alirocumab is a biopharmaceutical that obtained FDA approval in July 2015 as a second line treatment for high cholesterol in adults whose LDL-cholesterol (LDL-C) is not controlled by the combination of diet and statin treatment. It is a human monoclonal antibody part of the family of the PCSK9 inhibitors which are a novel class of anticholesterol therapeutics. From this family, it was the first agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety. PCSK9 inhibition facilitates more LDL-C clearance from the blood.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Protein Chemical Formula
C6472H9996N1736O2032S42
Protein Average Weight
146000.0 Da
Sequences
Not Available
Synonyms
  • Alirocumab
External IDs
  • REGN727
  • SAR236553

Pharmacology

Indication

Alirocumab is an antibody eliciting proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor activity that is indicated for:

(i) use in reducing the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease 4, and/or

(ii) use as an adjunct to diet or use alone or in combination with other lipid-lowering therapies (statins, ezetimibe, for example) for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C) levels in the body 4.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Adjunct therapy in management ofHeterozygous familial hypercholesterolemia (hefh)••••••••••••••••••••••••••
Adjunct therapy in management ofHeterozygous familial hypercholesterolemia (hefh)••••••••••••••••••••••••••
Adjunct therapy in management ofHomozygous familial hypercholesterolaemia (hofh)••••••••••••••••••••••••••
Prevention ofMyocardial infarction•••••••••••••••••••••••••••• •••••••••••••• ••••••••••••••••
Prevention ofStroke•••••••••••••••••••••••••••• •••••••••••••• ••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Alirocumab reduces levels of PCSK9 in a concentration-dependent manner.

Mechanism of action

Alirocumab is a fully human IgG1 monoclonal antibody that binds and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme found to have "gain of function" mutations in autosomal dominant hypercholesterolemia. PCSK9 is secreted by the liver and typically binds to the LDL receptors in serum and marks them for lysosomal degradation. In result, the LDL receptors are not able to recycle to the plasma membrane, reducing their binding to LDL-C and therefore reducing the clearance of LDL-C from plasma. Therefore by inhibiting PCSK9's actions, alirocumab allows for more LDL-C reuptake by the liver and facilitates a higher rate of clearance. Lower LDL cholesterol concentrations are associated with a reduced risk of coronary heart disease.

TargetActionsOrganism
AProprotein convertase subtilisin/kexin type 9
inhibitor
Humans
Absorption

Following subcutaneous (SC) administration, alirocumab is absorbed into the bloodstream and maximum concentrations are reached at a median time of 3-7 days. The absolute availability after SC administration was 85%.

Volume of distribution

Alirocumab is mainly distributed through the circulatory system, with minimal extravascular distribution.

Protein binding

Not Available

Metabolism

Antibodies are generally metabolized by the reticuloendothelial system and degraded into small peptides and individual amino acids - therefore specific metabolism studies were not conducted. Alirocumab did not show evidence of affecting CYP 450 enzymes or transporter proteins in co-administration with statins.

Route of elimination

Not Available

Half-life

In monotherapy, the median half-life of alirocumab at steady state was 17–20 days in patients receiving alirocumab at SC doses of 75 or 150 mg every 2 weeks. As statin therapy increases the production of PCSK9, statin co-administration is thought to shorten alirocumab half-life; therefore the median apparent half-life of alirocumab was reduced to 12 days at equivalent alirocumab doses. However, this difference is not considered clinically significant and does not change dosing recommendations.

Clearance

Not Available

Adverse Effects
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Toxicity

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 Alirocumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Alirocumab.
AducanumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Aducanumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Alirocumab.
AmivantamabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Amivantamab.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PraluentSolution75 mg / mLSubcutaneousSanofi Aventis2016-08-132021-03-04Canada flag
PraluentInjection, solution150 mgSubcutaneousSANOFI WINTHROP INDUSTRIE2021-03-03Not applicableEU flag
PraluentInjection, solution150 mg/1mLSubcutaneousRegeneron Pharmaceuticals, Inc.2019-02-15Not applicableUS flag
PraluentInjection, solution75 mgSubcutaneousSANOFI WINTHROP INDUSTRIE2021-03-03Not applicableEU flag
PraluentInjection, solution75 mg/1mLSubcutaneousSanofi US Corporation2019-02-15Not applicableUS flag

Categories

ATC Codes
C10AX14 — Alirocumab
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
Affected organisms
Not Available

Chemical Identifiers

UNII
PP0SHH6V16
CAS number
1245916-14-6

References

General References
  1. Farnier M: An evaluation of alirocumab for the treatment of hypercholesterolemia. Expert Rev Cardiovasc Ther. 2015 Dec;13(12):1307-23. doi: 10.1586/14779072.2015.1111759. Epub 2015 Nov 13. [Article]
  2. Devito F, Zito A, Ricci G, Carbonara R, Dentamaro I, Cortese F, Carbonara S, Ciccone MM: Focus on alirocumab: A PCSK9 antibody to treat hypercholesterolemia. Pharmacol Res. 2015 Dec;102:168-75. doi: 10.1016/j.phrs.2015.09.021. Epub 2015 Oct 8. [Article]
  3. Authors unspecified: Alirocumab (Praluent) to Lower LDL-Cholesterol. JAMA. 2015 Sep 22-29;314(12):1284-5. doi: 10.1001/jama.2015.11372. [Article]
  4. Alirocumab FDA Label 2019 [File]
KEGG Drug
D10335
PubChem Substance
347910431
RxNav
1659152
ChEMBL
CHEMBL2109540
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Alirocumab
FDA label
Download (967 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAcute Coronary Syndrome (ACS) / High Cholesterol1
4CompletedTreatmentDyslipidemia1
4CompletedTreatmentHigh Cholesterol1
4CompletedTreatmentHigh Cholesterol / Myocardial Infarction1
4CompletedTreatmentPeripheral Arterial Disease (PAD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionParenteral; Subcutaneous150 MG
Injection, solutionParenteral; Subcutaneous300 MG
Injection, solutionParenteral; Subcutaneous75 MG
Injection, solutionSubcutaneous150 mg/1mL
Injection, solutionSubcutaneous300 mg
Injection, solutionSubcutaneous75 mg/1mL
SolutionSubcutaneous150 mg / mL
SolutionSubcutaneous75 mg / mL
Injection, solution150 mg/nl
Injection, solution150 mg/ml
Injection, solutionSubcutaneous
Injection, solution75 mg/ml
Injection, solutionSubcutaneous150 mg/ml
Injection, solutionSubcutaneous75 mg/ml
Injection, solutionSubcutaneous150 mg
Injection, solutionSubcutaneous75 MG
SolutionSubcutaneous75 mg
SolutionSubcutaneous150 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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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. Devito F, Zito A, Ricci G, Carbonara R, Dentamaro I, Cortese F, Carbonara S, Ciccone MM: Focus on alirocumab: A PCSK9 antibody to treat hypercholesterolemia. Pharmacol Res. 2015 Dec;102:168-75. doi: 10.1016/j.phrs.2015.09.021. Epub 2015 Oct 8. [Article]

Drug created at November 11, 2015 20:54 / Updated at November 01, 2023 04:04