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
Download FASTA FormatReferences:
- NIH Inxight: Canakinumab [Link]
- 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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Adult onset still's disease •••••••••••• •••••• ••••••••• •••••••••• •••••••• Treatment of Cryopyrin-associated periodic syndromes (caps) •••••••••••• •••••• ••••••••• •••••••••• •••••••• Treatment of Familial cold autoinflammatory syndrome (fcas) •••••••••••• •••••• ••••••••• •••••••••• •••••••• Treatment of Familial mediterranean fever (fmf ) •••••••••••• •••••• ••••••••• •••••••••• •••••••• Treatment of Gout 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
Target Actions Organism AInterleukin-1 beta binderantibodyHumans - 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept 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. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Canakinumab. Abrocitinib The metabolism of Abrocitinib can be increased when combined with Canakinumab. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Canakinumab. - Food Interactions
- Take with or without food.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ilaris Solution 150 mg / mL Subcutaneous Novartis 2017-08-22 Not applicable Canada Ilaris Injection, powder, lyophilized, for solution 150 mg/1mL Subcutaneous Novartis Pharmaceuticals Corporation 2009-06-18 2020-02-29 US Ilaris Injection, powder, for solution 150 mg Subcutaneous Novartis Europharm Limited 2016-09-08 Not applicable EU Ilaris Powder, for solution 150 mg / vial Subcutaneous Novartis 2010-04-27 2020-01-13 Canada Ilaris Injection, solution 150 mg/ml Subcutaneous Novartis Europharm Limited 2020-12-16 Not applicable EU
Categories
- ATC Codes
- L04AC08 — Canakinumab
- Drug Categories
- Agents reducing cytokine levels
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunosuppressive Agents
- Interleukin Inhibitors
- Interleukin-1 Blockers
- Interleukin-1beta, antagonists & inhibitors
- Interleukin-1β Blockers
- Proteins
- Serum Globulins
- 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
- 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]
- 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]
- FDA Approved Drug Products: Ilaris (canakinumab) injection for subcutaneous administration (August 2023) [Link]
- Health Canada Product Monograph: Ilaris (canakinumab) solution for subcutaneous injection [Link]
- External Links
- KEGG Drug
- D09315
- PubChem Substance
- 347910340
- 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
Phase Status Purpose Conditions Count 4 Recruiting Prevention Coronavirus Disease 2019 (COVID‑19) / Psoriatic Arthritis / Rheumatoid Arthritis / Spondylarthritis 1 3 Active Not Recruiting Treatment Adult Onset Still's Disease 1 3 Active Not Recruiting Treatment Non-Small Cell Lung Cancer (NSCLC) 1 3 Active Not Recruiting Treatment Pancreatic Adenocarcinoma Metastatic / Pancreatic Metastatic Cancer 1 3 Completed Treatment Acute Gouty Arthritis Flares 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Subcutaneous 150 mg/ml 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 Parenteral; Subcutaneous 150 MG/ML Injection, solution Subcutaneous 150 mg/1mL Powder, for solution Subcutaneous 150 mg / vial Solution Subcutaneous 150 mg / mL Injection, solution Subcutaneous 150 mg/ml Injection, powder, for solution 150 MG Powder, for solution Subcutaneous 150 mg Solution Subcutaneous 150 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- BinderAntibody
- 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
Drug created at March 19, 2008 16:15 / Updated at April 19, 2024 20:55