Identification
NameCanakinumab
Accession NumberDB06168
TypeBiotech
GroupsApproved, Investigational
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 structureDb06168
Related Articles
Protein chemical formulaC6452H9958N1722O2010S42
Protein average weight145200.0 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
External IDs Not Available
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IlarisInjection, powder, for solution150 mgSubcutaneousNovartis Europharm Limited2009-10-23Not applicableEu
IlarisInjection, powder, lyophilized, for solution150 mg/mLSubcutaneousNovartis2009-06-18Not applicableUs
IlarisSolution150 mgSubcutaneousNovartisNot applicableNot applicableCanada
IlarisInjection, powder, for solution150 mgSubcutaneousNovartis Europharm Limited2009-10-23Not applicableEu
IlarisInjection, solution150 mg/mLSubcutaneousNovartis2016-12-22Not applicableUs
IlarisInjection, powder, for solution150 mgSubcutaneousNovartis Europharm Limited2009-10-23Not applicableEu
IlarisPowder, for solution150 mgSubcutaneousNovartis2010-04-27Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII37CQ2C7X93
CAS number914613-48-2
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).

TargetKindPharmacological actionActionsOrganismUniProt ID
Interleukin-1 betaProteinyes
binder
HumanP01584 details
Related Articles
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
PathwaysNot 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 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
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 risk or severity of adverse effects can be increased when Canakinumab is combined with G17DT.Investigational
GI-5005The risk or severity of adverse effects can be increased when Canakinumab is combined with GI-5005.Investigational
GolimumabThe risk or severity of adverse effects can be increased when Golimumab is combined with Canakinumab.Approved
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Canakinumab.Approved
INGN 201The risk or severity of adverse effects can be increased when Canakinumab is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Canakinumab is combined with INGN 225.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.Investigational
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Canakinumab is combined with Rabies vaccine.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Canakinumab.Approved
RindopepimutThe risk or severity of adverse effects can be increased when Canakinumab is combined with CDX-110.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Canakinumab.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Canakinumab.Approved
SRP 299The risk or severity of adverse effects can be increased when Canakinumab is combined with SRP 299.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Canakinumab.Approved, Investigational
TG4010The risk or severity of adverse effects can be increased when Canakinumab is combined with TG4010.Investigational
TofacitinibCanakinumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Canakinumab.Approved, Investigational
Food Interactions
  • No food effects were found.
References
Synthesis ReferenceNot Available
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
ATC CodesL04AC08 — Canakinumab
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (120 KB)
MSDSDownload (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
2CompletedTreatmentPeripheral Artery Disease (PAD)1
2CompletedTreatmentPyoderma Gangrenosum1
2CompletedTreatmentRheumatoid Arthritis4
2CompletedTreatmentSchnitzler's Syndrome2
2CompletedTreatmentTNF-receptor Associated Periodic Syndromes (TRAPS)1
2CompletedTreatmentType 2 Diabetes Mellitus1
2CompletedTreatmentUrticarias / Vasculitis1
2CompletedTreatmentSynovitis of osteoarthritis1
2Not Yet RecruitingTreatmentSickle Cell Disorders1
2RecruitingTreatmentAdult-Onset Still´s Disease1
2RecruitingTreatmentCardiovascular Disease (CVD) / HIV Disease1
2RecruitingTreatmentChronic Idiopathic Urticaria1
2RecruitingTreatmentSarcoidosis, Pulmonary1
2TerminatedNot AvailableAbdominal Aortic Aneurysms (AAA)1
2TerminatedTreatmentInflammatory Diseases / Polymyalgia Rheumatica1
2TerminatedTreatmentNonvalvular Atrial Fibrillation1
2WithdrawnTreatmentDiabetes Mellitus (DM) / Diabetes Type 11
2WithdrawnTreatmentMucocutaneous Lymph Node Syndrome1
2, 3TerminatedTreatmentType 2 Diabetes Mellitus1
3Active Not RecruitingTreatmentAtherosclerosis1
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
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
ManufacturersNot Available
PackagersNot 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
PricesNot Available
PatentsNot Available
Properties
StateLiquid
Experimental PropertiesNot Available
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot 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, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells.
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 August 17, 2016 12:24