Crizanlizumab
Identification
- Summary
Crizanlizumab is a monoclonal antibody that targets selectin to reduce the frequency of vasooclusive crises in patients with sickle cell disease.
- Brand Names
- Adakveo
- Generic Name
- Crizanlizumab
- DrugBank Accession Number
- DB15271
- Background
Crizanlizumab is a humanized IgG2 monoclonal antibody used to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease.9 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.8
Currently, patients are prescribed hydroxyurea to raise levels of fetal hemoglobin as a method of reducing morbidity and mortality.4 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.5 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15, 2019.9 While crizanlizumab received conditional marketing authorization from the EMA in October 2020, this approval was revoked in August 2023 due to concerns over the efficacy and safety of the drug.10
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 146000.0 Da (Theoretical)
- Sequences
- Not Available
- Synonyms
- Crizanlizumab
- crizanlizumab-tmca
- External IDs
- SEG101
Pharmacology
- Indication
Crizanlizumab is indicated to reduce the frequency of vaso-occlusive crisis in patients with sickle cell diseases who are ≥16 years old.9
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prevention of Vaso-occlusive crises •••••••••••• •••••• ••••••••• ••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Crizanlizumab is a P-selectin inhibitor that prevents interactions between endothelial cells, platelets, red blood cells, and leukocytes.9 It has a long duration of action as it is given every 4 weeks.9 Patients should be counselled regarding the risk of infusion reactions as well as crizanlizumab's interference with platelet counts using EDTA tubes.9
- 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.6,9 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.6,9 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.3
Target Actions Organism AP-selectin inhibitorHumans - Absorption
Crizanlizumab reaches a Cmax of 0.16mg/mL with an AUC of 34.6mg*hr/mL.9
- Volume of distribution
The volume of distribution of crizanlizumab is 4.26L.9
- Protein binding
- Metabolism
Crizanlizumab is expected to be metabolized into smaller peptides and amino acids.9
- Route of elimination
Monoclonal antibodies are eventually phagocytosed and broken down to smaller peptides and amino acids which are eliminated in a similar fashion to other proteins.1,2 Monoclonal antibodies are generally not eliminated in the urine, and only a small amount is excreted in bile.7
- 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.9
- Clearance
Given a 5mg/kg dose of crizanlizumab, the clearance rate is 11.7ml/hr in healthy subjects.9
- Adverse Effects
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- Toxicity
Data regarding the toxicity of crizanlizumab is not readily available.9
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Adakveo Injection 10 mg/1mL Intravenous Novartis Pharmaceuticals Corporation 2019-11-15 Not applicable US Adakveo Injection, solution, concentrate 10 mg/ml Intravenous Novartis Europharm Limited 2020-12-16 2023-09-29 EU
Categories
- ATC Codes
- B06AX01 — Crizanlizumab
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- L7451S9126
- CAS number
- 1690318-25-2
References
- General References
- Tabrizi MA, Tseng CM, Roskos LK: Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006 Jan;11(1-2):81-8. doi: 10.1016/S1359-6446(05)03638-X. [Article]
- Lobo ED, Hansen RJ, Balthasar JP: Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004 Nov;93(11):2645-68. doi: 10.1002/jps.20178. [Article]
- Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, Guthrie TH, Knight-Madden J, Alvarez OA, Gordeuk VR, Gualandro S, Colella MP, Smith WR, Rollins SA, Stocker JW, Rother RP: Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. N Engl J Med. 2017 Feb 2;376(5):429-439. doi: 10.1056/NEJMoa1611770. Epub 2016 Dec 3. [Article]
- Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, Orringer E, Bellevue R, Olivieri N, Eckman J, Varma M, Ramirez G, Adler B, Smith W, Carlos T, Ataga K, DeCastro L, Bigelow C, Saunthararajah Y, Telfer M, Vichinsky E, Claster S, Shurin S, Bridges K, Waclawiw M, Bonds D, Terrin M: Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA. 2003 Apr 2;289(13):1645-51. doi: 10.1001/jama.289.13.1645. [Article]
- Riley TR, Riley TT: Profile of crizanlizumab and its potential in the prevention of pain crises in sickle cell disease: evidence to date. J Blood Med. 2019 Aug 30;10:307-311. doi: 10.2147/JBM.S191423. eCollection 2019. [Article]
- Gardner RV: Sickle Cell Disease: Advances in Treatment. Ochsner J. 2018 Winter;18(4):377-389. doi: 10.31486/toj.18.0076. [Article]
- Ryman JT, Meibohm B: Pharmacokinetics of Monoclonal Antibodies. CPT Pharmacometrics Syst Pharmacol. 2017 Sep;6(9):576-588. doi: 10.1002/psp4.12224. Epub 2017 Jul 29. [Article]
- Ankit Mangla; Moavia Ehsan; Smita Maruvada (2019). Sickle Cell Anemia. Stat Pearls.
- FDA Approved Drug Products: Adakveo Crizanlizumab-TMCA Intravenous Injection [Link]
- BioSpace: EU Pulls Authorization of Novartis’ Sickle Cell Disease Drug [Link]
- External Links
- 2262421
- Wikipedia
- Crizanlizumab
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) 1 4 Completed Treatment Sickle Cell Disease (SCD) 1 4 Recruiting Treatment Sickle Cell Disease (SCD) 1 3 Active Not Recruiting Treatment Sickle Cell Disease (SCD) 1 2 Active Not Recruiting Treatment RVCL - Retinal Vasculopathy Cerebral Leukoencephalopathy 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 10 mg/1mL Injection, solution, concentrate Intravenous 10 MG/ML - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Sialic acid binding
- Specific Function
- Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligan...
- Gene Name
- SELP
- Uniprot ID
- P16109
- Uniprot Name
- P-selectin
- Molecular Weight
- 90833.105 Da
References
- FDA Approved Drug Products: Adakveo Crizanlizumab-TMCA Intravenous Injection [Link]
Drug created at May 20, 2019 15:06 / Updated at August 16, 2023 01:49