Canakinumab

Identification

Summary

Canakinumab is an interleukin-1β blocker used to treat Periodic Fever Syndromes such as Cryopyrin-Associated Periodic Syndromes (CAPS) and Familial Mediterranean Fever (FMF), and also to treat active Systemic Juvenile Idiopathic Arthritis (SJIA).

Brand Names
Ilaris
Generic Name
Canakinumab
DrugBank Accession Number
DB06168
Background

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
Protein Chemical Formula
C6452H9958N1722O2010S42
Protein Average Weight
145157.0 Da (deglycosylated)
Sequences
>HEAVY_CHAIN
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVAIIWYDGDNQYY
ADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARDLRTGPFDYWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGK
>LIGHT_CHAIN
EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQSFSGVPS
RFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPFTFGPGTKVDIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
References:
  1. NIH Inxight: Canakinumab [Link]
Download FASTA Format
Synonyms
  • Canakinumab
External IDs
  • ACZ-885
  • ACZ885

Pharmacology

Indication

Canakinumab is indicated for the treatment of periodic fever syndromes in specific patient populations. In patients ≥4 years of age, canakinumab is indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS). In adult and pediatric patients, canakinumab is also indicated for the treatment of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD), and Familial Mediterranean Fever (FMF).3

Canakinumab is additionally indicated in patients ≥2 years of age for the treatment of active Still's disease, including Adult-Onset Still's Disease (AOSD) and Systemic Juvenile Idiopathic Arthritis (SJIA).3

Canakinumab is also indicated for the treatment of gout flares in adult patients in whom standard therapies (e.g. NSAIDs, colchicine) are contraindicated, not tolerated, or ineffective, and in whom repeated courses of corticosteroids are not appropriate.3

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAdult onset still's disease•••••••••••••••••• ••••••••••••••••••• ••••••••
Treatment ofCryopyrin-associated periodic syndromes (caps)•••••••••••••••••• ••••••••••••••••••• ••••••••
Treatment ofFamilial cold autoinflammatory syndrome (fcas)•••••••••••••••••• ••••••••••••••••••• ••••••••
Treatment ofFamilial mediterranean fever (fmf )•••••••••••••••••• ••••••••••••••••••• ••••••••
Treatment ofGout flares••••••••••••••••••••••••••• ••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Canakinumab neutralizes the activity of human IL-1β, 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.3 The protein cryopyrin controls the activation of IL-1β, and mutations in cryopyrin's gene, NLRP-3, up-regulate IL-1β activation. 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).3

TargetActionsOrganism
AInterleukin-1 beta
binder
antibody
Humans
Absorption

The absolute bioavailability of subcutaneously administered canakinumab is estimated to be 66%.3 Peak serum concentration is 16 ± 3.5 mcg/mL and occurs approximately 7 days following a single subcutaneous dose of 150mg.3 Exposure to canakinumab increases proportionately to the administered dose.3

Volume of distribution

The steady-state volume of distribution of canakinumab is variable based on weight - it was estimated to be 6.01 liters in a typical CAPS patient weighing 70 kg, 3.2 liters in a SJIA patient weighing 33 kg, 6.34 liters for a Periodic Fever Syndrome (TRAPS, HIDS/MKD, FMF) patient weighing 70 kg and 7.9 liters in a typical patient with gout flares weighing 93 kg.3

Protein binding

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

Metabolism

Canakinumab, like other therapeutic proteins, is likely degraded via non-specific catabolic processes to smaller peptides and amino acids.

Route of elimination

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

Half-life

26 days

Clearance

The clearance of canakinumab is variable based on weight - it was estimated to be 0.174 L/day in a typical CAPS patient weighing 70 kg, 0.11 L/day in an SJIA patient weighing 33 kg, 0.17 L/day in a Periodic Fever Syndrome (TRAPS, HIDS/MKD, FMF) patient weighing 70 kg and 0.23 L/day in a typical patient with gout flares of body weight 93 kg.3

Adverse Effects
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Toxicity

There are no confirmed cases of overdosage with canakinumab.3 In the event of an overdose, the patient should be monitored closely and appropriate symptomatic treatment should be administered immediately as clinically indicated.

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.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Canakinumab.
AbrocitinibThe metabolism of Abrocitinib can be increased when combined with Canakinumab.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Canakinumab.
Food Interactions
  • Take with or without food.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IlarisInjection, solution150 mg/mlSubcutaneousNovartis Europharm Limited2020-12-16Not applicableEU flag
IlarisInjection, powder, for solution150 mgSubcutaneousNovartis Europharm Limited2016-09-08Not applicableEU flag
IlarisInjection, solution150 mg/1mLSubcutaneousNovartis Pharmaceuticals Corporation2016-12-22Not applicableUS flag
IlarisInjection, powder, for solution150 mgSubcutaneousNovartis Europharm Limited2016-09-082019-06-21EU flag
IlarisSolution150 mg / mLSubcutaneousNovartis2017-08-22Not applicableCanada flag

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
Affected organisms
  • Humans and other mammals

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. [Article]
  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. [Article]
  3. FDA Approved Drug Products: Ilaris (canakinumab) injection for subcutaneous administration (August 2023) [Link]
  4. Health Canada Product Monograph: Ilaris (canakinumab) solution for subcutaneous injection [Link]
KEGG Drug
D09315
PubChem Substance
347910340
RxNav
853491
ChEMBL
CHEMBL1201834
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Canakinumab
FDA label
Download (120 KB)
MSDS
Download (568 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingPreventionCoronavirus Disease 2019 (COVID‑19) / Psoriatic Arthritis / Rheumatoid Arthritis / Spondylarthritis1
3Active Not RecruitingTreatmentAdult Onset Still's Disease1
3Active Not RecruitingTreatmentNon-Small Cell Lung Cancer (NSCLC)1
3Active Not RecruitingTreatmentPancreatic Adenocarcinoma Metastatic / Pancreatic Metastatic Cancer1
3CompletedTreatmentAcute Gouty Arthritis Flares1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionSubcutaneous150 mg/ml
Injection, powder, for solutionParenteral; Subcutaneous150 MG
Injection, powder, for solutionSubcutaneous150 MG
Injection, powder, lyophilized, for solutionSubcutaneous150 mg/1mL
Injection, solutionParenteral; Subcutaneous150 MG/ML
Injection, solutionSubcutaneous150 mg/1mL
Powder, for solutionSubcutaneous150 mg / vial
SolutionSubcutaneous150 mg / mL
Injection, solutionSubcutaneous150 mg/ml
Injection, solutionSubcutaneous
Injection, powder, for solution150 MG
Powder, for solutionSubcutaneous150 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
Binder
Antibody
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. [Article]
  2. FDA Approved Drug Products: Ilaris (canakinumab) injection for subcutaneous administration (August 2023) [Link]

Drug created at March 19, 2008 16:15 / Updated at March 18, 2024 16:48