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| Primary information |
|---|
| ID | 15785 |
| Therapeutic ID | Th1628 |
| Protein Name | Crizanlizumab |
| Sequence | >Th1628_Crizanlizumab
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYDINWVRQAPGKGLEWMGWIYPGDGSIKYNEKFKGRVTMTVDKSTDTAYMELSSLRSEDTAVYYCARRGEYGNYEGAMDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVTSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGMEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCAVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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| Molecular Weight | 146000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Given a 5mg/kg dose of crizanlizumab, the mean terminal elimination half life of crizanlizumab is 10.6 days in healthy subjects and 7.6 days in patients with sickle cell disease.[L10097] |
| Description | Crizanlizumab is a humanized IgG2 monoclonal antibody used to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease.[L10097] Sickle cell disease is a genetically inherited condition prevalent in the Middle East, Africa, and certain parts of India. The genetic mutation associated with this disease leads to the formation of abnormal, sickle shaped red blood cells that aggregate and block blood vessels throughout the body, causing vaso-occlusive crises. Sickle cell disease can lead to excruciating pain, stroke, infection, and various other complications arising from the blockage of blood vessels.[T734] Currently, patients are prescribed [hydroxyurea] to raise levels of fetal hemoglobin as a method of reducing morbidity and mortality.[A187904] Though hydroxyurea has been shown to reduce the frequency of vaso-occlusive crises, adherence to this therapy is difficult due to adverse effects and the high variability of response to the drug between patients.[A187907] Crizanlizumab, or SEG101, is given once every 4 weeks and may improve patient adherence. It was developed by Novartis and was granted FDA approval on November 15, 2019.[L10097] |
| Indication/Disease | Crizanlizumab is indicated to reduce the frequency of vaso-occlusive crisis in patients with sickle cell diseases who are =16 years old.[L10097] |
| Pharmacodynamics | Crizanlizumab is a P-selectin inhibitor that prevents interactions between endothelial cells, platelets, red blood cells, and leukocytes.[L10097] It has a long duration of action as it is given every 4 weeks.[L10097] Patients should be counselled regarding the risk of infusion reactions as well as crizanlizumab's interference with platelet counts using EDTA tubes.[L10097] |
| Mechanism of Action | Crizanlizumab binds to P-selectin on endothelial cells and platelets, preventing their interaction with P-selectin glycoprotein ligand 1 on endothelial cells, platelets, red blood cells, and leukocytes.[A187910,L10097] By preventing this interaction, components of the blood are less likely to come together, causing a vaso-occlusive crisis in patients with sickle cell diseases.[A187910,L10097] The median per year incidence of vaso-occlusive crises was 1.04 in the high-dose crizanlizumab group, 2.00 in the low-dose crizanlizumab group, and 2.08 in the placebo group.[A187901] |
| Toxicity | Data regarding the toxicity of crizanlizumab is not readily available.[L10097] |
| Metabolism | Crizanlizumab is expected to be metabolized into smaller peptides and amino acids.[L10097] |
| Absorption | Crizanlizumab reaches a Cmax of 0.16mg/mL with an AUC of 34.6mg |
| The volume of distribution of crizanlizumab is 4.26L.[L10097] |
| Clearance | Given a 5mg/kg dose of crizanlizumab, the clearance rate is 11.7ml/hr in healthy subjects.[L10097] |
| Categories | Antibodies, Monoclonal, Humanized |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | P-selectin |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |