Identification

Name
Canakinumab
Accession Number
DB06168
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
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.

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
  • ACZ-885
  • ACZ885
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IlarisInjection, powder, for solution150 mgSubcutaneousNovartis Europharm Limited2009-10-23Not applicableEu
IlarisPowder, for solution150 mgSubcutaneousNovartis2010-04-27Not applicableCanada
IlarisInjection, solution150 mg/mLSubcutaneousNovartis2016-12-22Not applicableUs
IlarisInjection, powder, for solution150 mgSubcutaneousNovartis Europharm Limited2009-10-23Not applicableEu
IlarisSolution150 mgSubcutaneousNovartis2017-08-22Not applicableCanada
IlarisInjection, powder, for solution150 mgSubcutaneousNovartis Europharm Limited2009-10-23Not applicableEu
IlarisInjection, powder, lyophilized, for solution150 mg/mLSubcutaneousNovartis2009-06-18Not applicableUs
Categories
UNII
37CQ2C7X93
CAS number
914613-48-2

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).

Structured Indications
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
Human
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]
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
DrugInteractionDrug group
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Canakinumab.Approved
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Canakinumab.Investigational
AnakinraThe risk or severity of adverse effects can be increased when Anakinra is combined with Canakinumab.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Canakinumab.Investigational
Certolizumab pegolThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Canakinumab.Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Canakinumab.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Canakinumab.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Canakinumab.Approved
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Canakinumab.Approved, Investigational
FingolimodCanakinumab may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Canakinumab.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Canakinumab.Investigational
GolimumabThe risk or severity of adverse effects can be increased when Golimumab is combined with Canakinumab.Approved
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Canakinumab.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Canakinumab.Approved, Withdrawn
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Canakinumab.Approved
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Canakinumab.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Canakinumab.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Canakinumab is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Canakinumab is combined with Natalizumab.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Canakinumab.Approved, Investigational
PirfenidoneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with Canakinumab.Approved, Investigational
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Canakinumab.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Canakinumab.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Canakinumab.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Canakinumab.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Canakinumab.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Canakinumab.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Canakinumab.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Canakinumab.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Canakinumab.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Canakinumab.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Canakinumab.Investigational
TofacitinibCanakinumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Canakinumab.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Canakinumab.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Canakinumab.Approved
Food Interactions
  • No food effects were found.

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]
External Links
KEGG Drug
D09315
PubChem Substance
347910340
ChEMBL
CHEMBL1201834
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Canakinumab
ATC Codes
L04AC08 — Canakinumab
AHFS Codes
  • 92:44.00 — Immunosuppressive Agents
FDA label
Download (120 KB)
MSDS
Download (568 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentWet Age-Related Macular Degeneration1
1Not Yet RecruitingTreatmentPeriodic Fever1
1RecruitingTreatmentColorectal Cancer, Triple Negative Breast Cancer, NSCLC - Adenocarcinoma / Colorectal Cancers / Non-small Cell Lung Cancer (Adenocarcinoma) / Triple Negative Breast Cancer (TNBC)1
1TerminatedTreatmentProliferative Diabetic Retinopathy (PDR)1
1, 2CompletedBasic ScienceChronic Obstructive Pulmonary Disease (COPD)1
1, 2CompletedTreatmentArthritis, Juvenile Rheumatoid1
1, 2CompletedTreatmentRheumatoid Arthritis1
1, 2TerminatedTreatmentRheumatoid Arthritis1
2Active Not RecruitingTreatmentSchnitzler's Syndrome1
2CompletedPreventionGout Acute1
2CompletedTreatmentAcute Gouty Arthritis1
2CompletedTreatmentAtherosclerosis / Prediabetic State / Type 2 Diabetes Mellitus1
2CompletedTreatmentCanakinumab in Type 1 Diabetes / Diabetes, Diabetes Mellitus Type 1 / Newly Diagnosed Type 1 Diabetes / Preservation of Insulin Secretion1
2CompletedTreatmentColchicine Resistant/Intolerant Familial Mediterranean Fever1
2CompletedTreatmentEye Dryness1
2CompletedTreatmentFamilial Mediterranean Fever (FMF )1
2CompletedTreatmentGout Acute2
2CompletedTreatmentImpaired Glucose Tolerance (IGT) / Type 2 Diabetes Mellitus1
2CompletedTreatmentMevalonate Kinase Deficiency1
2CompletedTreatmentNALP3 Mutation1
2CompletedTreatmentOsteoarthritis (OA)1
2CompletedTreatmentPyoderma Gangrenosum1
2CompletedTreatmentRheumatoid Arthritis4
2CompletedTreatmentSchnitzler's Syndrome2
2CompletedTreatmentTNF-receptor Associated Periodic Syndromes (TRAPS)1
2CompletedTreatmentType 2 Diabetes Mellitus1
2CompletedTreatmentUrticarias / Vasculitis1
2RecruitingTreatmentAdult-Onset Still´s Disease1
2RecruitingTreatmentCardiovascular Disease (CVD) / Human Immunodeficiency Virus (HIV)1
2RecruitingTreatmentChronic Idiopathic Urticaria1
2RecruitingTreatmentSarcoidosis, Pulmonary1
2RecruitingTreatmentSickle Cell Disorders1
2TerminatedNot AvailableAbdominal Aortic Aneurysms (AAA)1
2TerminatedTreatmentInflammatory Diseases / Polymyalgia Rheumatica1
2TerminatedTreatmentNonvalvular Atrial Fibrillation1
2TerminatedTreatmentPeripheral Artery Disease (PAD)1
2WithdrawnTreatmentDiabetes Mellitus (DM) / Diabetes Type 11
2WithdrawnTreatmentMucocutaneous Lymph Node Syndrome1
2, 3TerminatedTreatmentType 2 Diabetes Mellitus1
3Active Not RecruitingTreatmentHereditary Periodic Fevers1
3Active Not RecruitingTreatmentSystemic Juvenile Idiopathic Arthritis (SJIA)1
3CompletedTreatmentAcute Gouty Arthritis1
3CompletedTreatmentAcute Gouty Arthritis Flares / Chronic Gouty Arthritis1
3CompletedTreatmentCryopyrin-associated Periodic Syndromes (CAPS)1
3CompletedTreatmentCryopyrin-associated Periodic Syndromes (CAPS) / Familial Cold Autoinflammatory Syndrome (FCAS) / Muckle Wells Syndrome / Neonatal Onset Multisystem Inflammatory Disease1
3CompletedTreatmentCryopyrin-associated Periodic Syndromes (CAPS) / Familial Cold Autoinflammatory Syndrome (FCAS) / Muckle-Wells Syndrome (MWS) / Neonatal Onset Multisystem Inflammatory Disease3
3CompletedTreatmentGout Acute2
3CompletedTreatmentMuckle Wells Syndrome1
3CompletedTreatmentPeriodic Fevers Syndrome1
3CompletedTreatmentSystemic Juvenile Idiopathic Arthritis (SJIA)1
3CompletedTreatmentSystemic Juvenile Idiopathic Arthritis With Active Flare1
3RecruitingTreatmentAtherosclerosis1
3RecruitingTreatmentHereditary Periodic Fevers / Systemic Juvenile Idiopathic Arthritis (SJIA)1
3RecruitingTreatmentSystemic Juvenile Idiopathic Arthritis (SJIA)1
3TerminatedTreatmentAcute Gouty Arthritis1
3TerminatedTreatmentNeonatal-onset multisystemic inflammatory disease1
3TerminatedTreatmentSystemic Juvenile Idiopathic Arthritis (SJIA)1
3WithdrawnTreatmentAcute Gouty Arthritis1
3WithdrawnTreatmentSystemic Juvenile Idiopathic Arthritis (SJIA)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionSubcutaneous150 mg
Injection, powder, lyophilized, for solutionSubcutaneous150 mg/mL
Injection, solutionSubcutaneous150 mg/mL
Powder, for solutionSubcutaneous150 mg
SolutionSubcutaneous150 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
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 November 19, 2017 20:34