| Primary information |
|---|
| ThPP ID | Th1222 |
| Therapeutic Peptide/Protein Name | Canakinumab |
| Sequence | H-GAMMA-1 Chain: QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYG view full sequnce in fasta |
| Functional Classification | IIa |
| Molecular Weight | 145200 |
| Chemical Formula | C6452H9958N1722O2010S42 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting Point (℃) | NA |
| Half Life | 26 days |
| 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. |
| Indication/Disease | 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). |
| 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). |
| 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. |
| Metabolism | The metabolism of canakinumab is not yet determined. |
| Absorption | The absolute bioavailability of subcutaneous canakinumab is estimated to be 70%. |
| Volume of Distribution | 6.01 L |
| Clearance | 0.174 L/day [typical CAPS patient weighing 70 kg] |
| Categories | Antineoplastic and Immunomodulating Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | The risk or severity of adverse effects can be increased when Canakinumab is combined with Adalimumab, Afelimomab, Anakinra, BCG, Certolizumab pegol, Denosumab, Etanercept, Fingolimod, G17DT, GI-5005 etc |
| Target | Interleukin-1 beta |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Ilaris |
| Company | Novartis |
| Brand Discription | Ilaris (canakinumab) is a monoclonal antibody that blocks certain proteins in the body that can affect inflammation and other immune responses. |
| Prescribed for | Ilaris is used to treat certain types of periodic fever syndromes, sometimes called auto-inflammatory syndromes. |
| Chemical Name | NA |
| Formulation | Each vial of sterile, white, preservative-free, lyophilized powder contains canakinumab 150Â mg. Nonmedicinal ingredients: sucrose, L-histidine, L-histidine HCL monohydrate, polysorbate 80. |
| Physcial Appearnce | Lyphilized powder |
| Route of Administration | Subcutaneous |
| Recommended Dosage | The recommended dose of Ilaris is 150 mg for CAPS patients with body weight greater than 40 kg. For CAPS patients with body weight greater than or equal to 15 kg and less than or equal to 40 kg, the recommended dose is 2 mg/kg. For children 15 to 40 kg with an inadequate response, the dose can be increased to 3 mg |
| Contraindication | Confirmed hypersensitivity to the active substance or to any of the excipients. |
| Side Effects | The most common adverse reactionsgreater than 10% reported by patients treated with ILARISare nasopharyngitis, diarrhea, influenza, rhinitis, nausea, headache, bronchitis, gastroenteritis, pharyngitis, weight increased, musculoskeletal pain, and vertigo. |
| Useful Link | https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/ilaris.pdf , https://www.drugs.com/ilaris.html , http://www.medbroadcast.com/drug/getdrug/ilaris |
| PubMed ID | 19169963, 19494217 |
| 3-D Structure | N.A. |