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| Primary information |
|---|
| ID | 10565 |
| Therapeutic ID | Th1116 |
| Protein Name | Canakinumab |
| Sequence | >Th1116_Canakinumab
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVAIIWYDGDNQYYADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARDLRTGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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| Molecular Weight | 145200 (deglycosylated) |
| Chemical Formula | C6452H9958N1722O2010S42 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 26 days |
| Description | Canakinumab is a recombinant (from murine Sp2/0-Ag14 cell line), human anti-human-IL-1β monoclonal antibody that belongs to the IgG1/κ isotype subclass. It comprises of two 447- or 448-residue heavy chains and two 214-residue light chains. Both heavy chains of canakinumab contain oligosaccharide chains linked to the protein backbone at N298. It binds to human IL-1β, thereby neutralizing its inflammatory activity by preventing its interaction with IL-1 receptors. However it does not bind IL-1alpha or IL-1 receptor antagonist (IL-1ra). It is marketed under the brand name Ilaris. |
| Indication/Disease | For the treatment of patients aged 4 years 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). It is also used to treat systemic juvenile idiopathic arthritis (SJIA) in patients pf age 2 years and older . It can be effectively afe and effective, offerin and is therefore considered a significantly better option cted daily and which is often poorly tolerated by the young patients |
| 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%. |
| 6.01 L [typical CAPS patient weighing 70 kg] |
| Clearance | 0.174 L/day [typical CAPS patient weighing 70 kg] |
| Categories | Anti-Inflammatory Agents and Monoclonal antibodies |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-1 beta |
| Brand Name | ILARIS |
| Company | Novartis Pharmaceuticals |
| Brand Description | Novartis Pharmaceuticals |
| Prescribed For | Cryopyrin-Associated Periodic Syndromes (CAPS), Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), Systemic Juvenile Idiopathic Arthritis (SJIA) |
| Chemical Name | NA |
| Formulation | Reconstitution with 1 mL of preservative-free Sterile Water for Injection is required prior to subcutaneous administration of the drug. The reconstituted canakinumab is a 150 mg/mL solution essentially free of particulates, clear to slightly opalescent, and is colorless or may have a slightly brownish-yellow tint. A volume of up to 1 mL can be withdrawn for delivery of 150 mg/mL canakinumab for subcutaneous administration. Each reconstituted vial contains 180 mg canakinumab, sucrose, L-histidine, L-histidine HCL monohydrate, polysorbate 80 and Sterile Water for Injection. No preservatives are present. |
| Physical Appearance | 180 mg of canakinumab as a white, preservative-free, lyophilized powder |
| Route of Administration | Subcutaneous |
| Recommended Dosage | Cryopyrin-Associated Periodic Syndromes (CAPS): 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/kg. Systemic Juvenile Idiopathic Arthritis (SJIA): The recommended dose of ILARIS for SJIA patients with a body weight greater than or equal to 7.5 kg is 4mg/kg (with a maximum of 300 mg) administered every four weeks via subcutaneous injection. |
| Contraindication | Confirmed hypersensitivity to the active substance or to any of the excipients. |
| Side Effects | ILARIS has been associated with an increased risk of serious infections, Immunosuppression, Hypersensitivity , Live vaccines should not be given concurrently with ILARIS. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |