Canakinumab

Identification

Name
Canakinumab
Accession Number
DB06168
Description

Canakinumab is a recombinant, human anti-human-IL-1β monoclonal antibody that belongs to the IgG1/κ isotype subclass. It is expressed in a murine Sp2/0-Ag14 cell line and comprised of two 447- (or 448-) residue heavy chains and two 214-residue light chains, with a molecular mass of 145157 Daltons when deglycosylated. Both heavy chains of canakinumab contain oligosaccharide chains linked to the protein backbone at asparagine 298 (Asn 298). Canakinumab binds to human IL-1β and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1alpha or IL-1 receptor antagonist (IL-1ra). Canakinumab is marketed under the brand name Ilaris and indicated for patients 4 years of age and older to treat Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), which are both part of the Cryopyrin-Associated Periodic Syndromes (CAPS) as well as for patients 2 years of age and older to treat systemic juvenile idiopathic arthritis (SJIA). Clinical trials have established the administration of canakinumab every 2 weeks to be safe and effective, offering a considerable advantage over the existing treatment with the human IL-1 receptor antagonist, anakinra, which must be injected daily and which is often poorly tolerated by patients.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Db06168
Protein Chemical Formula
C6452H9958N1722O2010S42
Protein Average Weight
145200.0 Da
Sequences
>8836_H|canakinumab|Homo sapiens||H-GAMMA-1 (VH(1-118)+CH1(119-216)+HINGE-REGION(217-231)+CH2(232-341)+CH3(342-448))|||||||448||||MW 49253.6|MW 49253.6|
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVAIIWYDGDNQYY
ADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARDLRTGPFDYWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGK
>8836_L|canakinumab|Homo sapiens||L-KAPPA (V-KAPPA(1-107)+C-KAPPA(108-214))|||||||214||||MW 23357.9|MW 23357.9|
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVAIIWYDGDNQYY
ADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARDLRTGPFDYWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQSFSGVPS
RFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPFTFGPGTKVDIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
Not Available
External IDs
  • ACZ-885
  • ACZ885

Pharmacology

Indication

Used in patients 4 years of age and older to treat Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), which are both part of the Cryopyrin-Associated Periodic Syndromes (CAPS) as well as for patients 2 years of age and older to treat systemic juvenile idiopathic arthritis (SJIA).

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Novartis AG has developed canakinumab as a subcutaneous injection and fully human mAb that neutralizes the bioactivity of human IL-1beta, which is involved in several inflammatory disorders. Canakinumab has promising clinical safety and pharmacokinetic properties, and demonstrated potential for the treatment of cryopyrin-associated periodic syndromes (CAPS), systemic juvenile idiopathic arthritis (SJIA), and possibly for other complex inflammatory diseases, such as rheumatoid arthritis, COPD disease and ocular diseases.

Mechanism of action

In inflammatory diseases involving Cryopyrin-Associated Periodic Syndromes (CAPS), interleukin-1 beta (IL-1β) is excessively activated and drives inflammation. The protein cryopyrin controls the activation of IL-1β, and mutations in cryopyrin's gene, NLRP-3, up-regulate IL-1β activation. Canakinumab is a human monoclonal anti-human IL-1β antibody of the IgG1/κ isotype. Canakinumab binds to human IL-1β and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1α or IL-1 receptor antagonist (IL-1ra).

TargetActionsOrganism
AInterleukin-1 beta
binder
Humans
Absorption

The absolute bioavailability of subcutaneous canakinumab is estimated to be 70%.

Volume of distribution
  • 6.01 L [typical CAPS patient weighing 70 kg]
Protein binding

Canakinumab binds to plasma IL-1β, but plasma protein binding was not quantified.

Metabolism

The metabolism of canakinumab is not yet determined.

Route of elimination

The route of elimination for canakinumab has not yet been determined.

Half-life

26 days

Clearance
  • 0.174 L/day [typical CAPS patient weighing 70 kg]
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

The most common adverse reactions involved the central nervous system (headache and vertigo), gastrointestinal system (diarrhea and nausea), neuromuscular and skeletal system (musculoskeletal pain), and respiratory system (rhinitis, nasopharyngitis and bronchitis). Influenza was also reported.

Affected organisms
  • Humans and other mammals
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
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Canakinumab.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Canakinumab.
AbirateroneThe metabolism of Abiraterone can be increased when combined with Canakinumab.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Canakinumab.
AcebutololThe metabolism of Acebutolol can be increased when combined with Canakinumab.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Canakinumab.
AcetaminophenThe metabolism of Acetaminophen can be increased when combined with Canakinumab.
AcetohexamideThe metabolism of Acetohexamide can be increased when combined with Canakinumab.
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be increased when combined with Canakinumab.
AcyclovirThe metabolism of Acyclovir can be increased when combined with Canakinumab.
Additional Data Available
  • Extended Description
    Extended Description

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

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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
  • Take with or without food.

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IlarisInjection, powder, for solution150 mgSubcutaneousNovartis Europharm Limited2009-10-23Not applicableEU flag
IlarisPowder, for solution150 mgSubcutaneousNovartis2010-04-272020-01-13Canada flag
IlarisInjection, powder, for solution150 mgSubcutaneousNovartis Europharm Limited2009-10-23Not applicableEU flag
IlarisInjection, solution150 mg/1mLSubcutaneousNovartis Pharmaceuticals Corporation2016-12-22Not applicableUS flag
IlarisInjection, powder, for solution150 mgSubcutaneousNovartis Europharm Limited2009-10-23Not applicableEU flag
IlarisSolution150 mgSubcutaneousNovartis2017-08-22Not applicableCanada flag
IlarisInjection, powder, lyophilized, for solution150 mg/1mLSubcutaneousNovartis Pharmaceuticals Corporation2009-06-182020-02-29US flag
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

ATC Codes
L04AC08 — Canakinumab
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
37CQ2C7X93
CAS number
914613-48-2

References

General References
  1. Church LD, McDermott MF: Canakinumab, a fully-human mAb against IL-1beta for the potential treatment of inflammatory disorders. Curr Opin Mol Ther. 2009 Feb;11(1):81-9. [PubMed:19169963]
  2. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN: Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009 Jun 4;360(23):2416-25. doi: 10.1056/NEJMoa0810787. [PubMed:19494217]
KEGG Drug
D09315
PubChem Substance
347910340
RxNav
853491
ChEMBL
CHEMBL1201834
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Canakinumab
AHFS Codes
  • 92:44.00 — Immunosuppressive Agents
FDA label
Download (120 KB)
MSDS
Download (568 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
3Active Not RecruitingTreatmentNon-Small-Cell Lung1
3Active Not RecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19) / Pneumonia and Cytokine Release Syndrome (Covid-19)1
3CompletedTreatmentAcute Gouty Arthritis4
3CompletedTreatmentAcute Gouty Arthritis Flares1
3CompletedTreatmentAtherosclerosis1
3CompletedTreatmentCryopyrin-associated Periodic Syndromes (CAPS)1
3CompletedTreatmentCryopyrin-associated Periodic Syndromes (CAPS) / Familial Cold Autoinflammatory Syndrome (FCAS) / Muckle Wells Syndrome / Muckle-Wells Syndrome (MWS) / Neonatal-Onset Multisystem Inflammatory Disease (NOMID)1
3CompletedTreatmentCryopyrin-associated Periodic Syndromes (CAPS) / Familial Cold Autoinflammatory Syndrome (FCAS) / Muckle-Wells Syndrome (MWS) / Neonatal-Onset Multisystem Inflammatory Disease (NOMID)3
3CompletedTreatmentHereditary Periodic Fevers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionSubcutaneous150 mg/ml
Injection, powder, for solution150 mg
Injection, powder, for solutionCutaneous150 MG
Injection, powder, for solutionParenteral; Subcutaneous150 MG
Injection, powder, for solutionSubcutaneous150 mg
Injection, powder, lyophilized, for solutionSubcutaneous150 mg/1mL
Injection, solutionCutaneous; Parenteral150 MG/ML
Injection, solutionSubcutaneous150 mg/1mL
Powder, for solutionSubcutaneous150 mg
SolutionSubcutaneous150 mg
Injection150 mg/ml
Powder
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
General Function
Protein domain specific binding
Specific Function
Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, ...
Gene Name
IL1B
Uniprot ID
P01584
Uniprot Name
Interleukin-1 beta
Molecular Weight
30747.7 Da
References
  1. Church LD, McDermott MF: Canakinumab, a fully-human mAb against IL-1beta for the potential treatment of inflammatory disorders. Curr Opin Mol Ther. 2009 Feb;11(1):81-9. [PubMed:19169963]

Drug created on March 19, 2008 10:15 / Updated on October 21, 2020 01:55

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