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

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).

Target	Actions	Organism
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.

Drug	Interaction
Unlock Additional Data
Abatacept	The risk or severity of adverse effects can be increased when Abatacept is combined with Canakinumab.
Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Canakinumab.
Abiraterone	The metabolism of Abiraterone can be increased when combined with Canakinumab.
Acalabrutinib	The metabolism of Acalabrutinib can be increased when combined with Canakinumab.
Acebutolol	The metabolism of Acebutolol can be increased when combined with Canakinumab.
Acenocoumarol	The metabolism of Acenocoumarol can be increased when combined with Canakinumab.
Acetaminophen	The metabolism of Acetaminophen can be increased when combined with Canakinumab.
Acetohexamide	The metabolism of Acetohexamide can be increased when combined with Canakinumab.
Acetylsalicylic acid	The metabolism of Acetylsalicylic acid can be increased when combined with Canakinumab.
Acyclovir	The metabolism of Acyclovir can be increased when combined with Canakinumab.

Additional Data Available

Extended Description

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

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Severity

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

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Evidence Level

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

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Action

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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

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Ilaris	Injection, solution	150 mg/1mL	Subcutaneous	Novartis Pharmaceuticals Corporation	2016-12-22	Not applicable
Ilaris	Injection, powder, for solution	150 mg	Subcutaneous	Novartis Europharm Limited	2009-10-23	Not applicable
Ilaris	Solution	150 mg	Subcutaneous	Novartis	2017-08-22	Not applicable
Ilaris	Injection, powder, lyophilized, for solution	150 mg/1mL	Subcutaneous	Novartis Pharmaceuticals Corporation	2009-06-18	2020-02-29
Ilaris	Injection, powder, for solution	150 mg	Subcutaneous	Novartis Europharm Limited	2009-10-23	Not applicable
Ilaris	Injection, powder, for solution	150 mg	Subcutaneous	Novartis Europharm Limited	2009-10-23	Not applicable
Ilaris	Powder, for solution	150 mg	Subcutaneous	Novartis	2010-04-27	2020-01-13

Additional Data Available

Application Number

Available for Purchase

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

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Product Code

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

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Chemical Identifiers

UNII: 37CQ2C7X93
CAS number: 914613-48-2

References

General References

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]
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]

External Links

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

Phase	Status	Purpose	Conditions	Count
3	Active Not Recruiting	Treatment	Non-Small Cell Lung Carcinoma (NSCLC)	1
3	Active Not Recruiting	Treatment	Non-Small-Cell Lung	1
3	Active Not Recruiting	Treatment	Novel Coronavirus Infectious Disease (COVID-19) / Pneumonia and Cytokine Release Syndrome (Covid-19)	1
3	Completed	Treatment	Acute Gouty Arthritis	4
3	Completed	Treatment	Acute Gouty Arthritis Flares	1
3	Completed	Treatment	Atherosclerosis	1
3	Completed	Treatment	Cryopyrin-associated Periodic Syndromes (CAPS)	1
3	Completed	Treatment	Cryopyrin-associated Periodic Syndromes (CAPS) / Familial Cold Autoinflammatory Syndrome (FCAS) / Muckle Wells Syndrome / Muckle-Wells Syndrome (MWS) / Neonatal-Onset Multisystem Inflammatory Disease (NOMID)	1
3	Completed	Treatment	Cryopyrin-associated Periodic Syndromes (CAPS) / Familial Cold Autoinflammatory Syndrome (FCAS) / Muckle-Wells Syndrome (MWS) / Neonatal-Onset Multisystem Inflammatory Disease (NOMID)	3
3	Completed	Treatment	Hereditary Periodic Fevers	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection	Subcutaneous	150 mg/ml
Injection, powder, for solution	Cutaneous	150 MG
Injection, powder, for solution	Parenteral; Subcutaneous	150 MG
Injection, powder, for solution	Subcutaneous	150 mg
Injection, powder, lyophilized, for solution	Subcutaneous	150 mg/1mL
Injection, solution	Cutaneous; Parenteral	150 MG/ML
Injection, solution	Subcutaneous	150 mg/1mL
Powder, for solution	Subcutaneous	150 mg
Solution	Subcutaneous	150 mg
Powder

Prices

Not Available

Patents

Not Available

Properties

State: Liquid
Experimental Properties: Not Available

Targets

Details1. Interleukin-1 beta

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

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]