Identification

Name
Alirocumab
Accession Number
DB09302
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Alirocumab is a biopharmaceutical drug approved by the FDA in July 2015 as a second line treatment for high cholesterol for adults whose LDL-cholesterol (LDL-C) is not controlled by diet and statin treatment. It is a human monoclonal antibody administered by subcutaneous injection that belongs to a novel class of anti-cholesterol drugs, known as PCSK9 inhibitors, and it was the first such 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.

Protein structure
Db09302
Protein chemical formula
C6472H9996N1736O2032S42
Protein average weight
146000.0 Da
Sequences
Not Available
Synonyms
Not Available
External IDs
REGN727 / SAR236553
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PraluentInjection, solution75 mgSubcutaneousSanofi Aventis Groupe2015-09-23Not applicableEu
PraluentInjection, solution75 mg/1mLSubcutaneoussanofi-aventis U.S. LLC2015-07-24Not applicableUs
PraluentInjection, solution75 mgSubcutaneousSanofi Aventis Groupe2015-09-23Not applicableEu
PraluentSolution150 mgSubcutaneousSanofi Aventis2016-04-29Not applicableCanada
PraluentInjection, solution150 mgSubcutaneousSanofi Aventis Groupe2015-09-23Not applicableEu
PraluentInjection, solution150 mgSubcutaneousSanofi Aventis Groupe2015-09-23Not applicableEu
PraluentInjection, solution75 mgSubcutaneousSanofi Aventis Groupe2015-09-23Not applicableEu
PraluentInjection, solution75 mg/1mLSubcutaneoussanofi-aventis U.S. LLC2015-07-24Not applicableUs
PraluentSolution150 mgSubcutaneousSanofi Aventis2016-08-13Not applicableCanada
PraluentInjection, solution75 mgSubcutaneousSanofi Aventis Groupe2015-09-23Not applicableEu
Categories
UNII
PP0SHH6V16
CAS number
1245916-14-6

Pharmacology

Indication

Alirocumab is indicated as an adjunct to diet and maximally tolerated statin therapy in adults who require additional LDL-cholesterol (LDL-C) lowering due to heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease.

Associated Conditions
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
Human
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Alirocumab.
AbituzumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Abituzumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Alirocumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Alirocumab.
AducanumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Aducanumab.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Alirocumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Alirocumab.
AmatuximabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Amatuximab.
AMG 108The risk or severity of adverse effects can be increased when AMG 108 is combined with Alirocumab.
AnifrolumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Anifrolumab.
Food Interactions
Not Available

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. [PubMed:26563849]
  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. [PubMed:26455563]
  3. Authors unspecified: Alirocumab (Praluent) to Lower LDL-Cholesterol. JAMA. 2015 Sep 22-29;314(12):1284-5. doi: 10.1001/jama.2015.11372. [PubMed:26393853]
External Links
KEGG Drug
D10335
PubChem Substance
347910431
ChEMBL
CHEMBL2109540
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Alirocumab
AHFS Codes
  • 24:06.24 — Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Inhibitors
FDA label
Download (967 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentIntracranial Atherosclerosis / Intraplaque Hemorrhage / Strokes1
1Active Not RecruitingBasic ScienceAtherosclerosis / Coronary Heart Disease (CHD)1
1CompletedBasic ScienceHigh Cholesterol4
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentHigh Cholesterol6
2Active Not RecruitingTreatmentHigh Cholesterol1
2CompletedTreatmentHigh Cholesterol5
2Not Yet RecruitingPreventionAcute Coronary Syndromes (ACS) / Dyslipidemias / High Cholesterol / Hyperlipidemias / Physiological Effects of Drugs / ST Elevation Myocardial Infarction1
2Not Yet RecruitingTreatmentVasculopathy1
2Unknown StatusTreatmentHigh Cholesterol1
2, 3Not Yet RecruitingTreatmentSepsis / Shock, Septic1
3Active Not RecruitingTreatmentHigh Cholesterol2
3CompletedPreventionAcute Coronary Syndromes (ACS)1
3CompletedTreatmentHeterozygous Familial Hypercholesterolemia2
3CompletedTreatmentHigh Cholesterol16
3Not Yet RecruitingTreatmentType2 Diabetes1
3RecruitingTreatmentAtheroma; Myocardial / Coronary Circulation / Coronary Vessel1
3RecruitingTreatmentAtherosclerotic Disease / Hemodialysis Treatment / High Cholesterol / Peritoneal dialysis therapy1
3RecruitingTreatmentCardiovascular Disease (CVD) / Dyslipidemias / Human Immunodeficiency Virus (HIV) Infections1
3RecruitingTreatmentHigh Cholesterol2
3RecruitingTreatmentHomozygous Familial Hypercholesterolemia1
4Active Not RecruitingTreatmentHigh Cholesterol1
4Active Not RecruitingTreatmentHigh Cholesterol / Myocardial Infarction1
4CompletedTreatmentAcute Coronary Syndromes (ACS) / High Cholesterol1
4CompletedTreatmentDyslipidemias1
4Not Yet RecruitingTreatmentHeterozygous Familial Hypercholesterolemia / Non-familial hypercholesterolemia1
4RecruitingTreatmentAtherosclerosis / Hyperlipidemias1
4RecruitingTreatmentCoronary Artery Disease / Thin-cap fIbroatheroma1
4RecruitingTreatmentPeripheral Arterial Disease (PAD)1
Not AvailableRecruitingNot AvailableCoronary Artery Disease Progression1
Not AvailableRecruitingNot AvailableDyslipoproteinemias1
Not AvailableRecruitingNot AvailableHigh Cholesterol1
Not AvailableRecruitingBasic ScienceAtherosclerosis / Cardiovascular Disease (CVD)1
Not AvailableRecruitingTreatmentGlomerulonephritis minimal lesion1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous150 mg/1mL
Injection, solutionSubcutaneous150 mg
Injection, solutionSubcutaneous75 mg
Injection, solutionSubcutaneous75 mg/1mL
SolutionSubcutaneous150 mg
SolutionSubcutaneous75 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

Targets

Kind
Protein
Organism
Human
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. [PubMed:26455563]

Drug created on November 11, 2015 13:54 / Updated on November 17, 2018 04:48