NAV

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

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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Associated Conditions
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

TargetActionsOrganism
AP-selectin
inhibitor
Humans
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

Monoclonal antibodies are generally not protein bound1,2.

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

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdakveoInjection10 mg/1mLIntravenousNovartis Pharmaceuticals Corporation2019-11-15Not applicableUS flag
AdakveoInjection, solution, concentrate10 mg/mlIntravenousNovartis Europharm Limited2020-12-16Not applicableEU flag

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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. Gardner RV: Sickle Cell Disease: Advances in Treatment. Ochsner J. 2018 Winter;18(4):377-389. doi: 10.31486/toj.18.0076. [Article]
  7. 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]
  8. Ankit Mangla; Moavia Ehsan; Smita Maruvada (2019). Sickle Cell Anemia. Stat Pearls.
  9. FDA Approved Drug Products: Adakveo Crizanlizumab-TMCA Intravenous Injection [Link]
RxNav
2262421
Wikipedia
Crizanlizumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentSickle Cell Disease (SCD)1
4RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19)1
4RecruitingTreatmentSickle Cell Disease (SCD)1
3Active Not RecruitingTreatmentSickle Cell Disease (SCD)1
2Active Not RecruitingTreatmentRVCL - Retinal Vasculopathy Cerebral Leukoencephalopathy1
2Active Not RecruitingTreatmentSickle Cell Disease (SCD)2
2CompletedTreatmentCoronavirus Disease 2019 (COVID‑19)1
2RecruitingTreatmentPriapism1
2RecruitingTreatmentSickle Cell Disease (SCD)1
1, 2Active Not RecruitingTreatmentMyelofibrosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous10 mg/1mL
Injection, solution, concentrateIntravenous10 MG/ML
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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Details1. P-selectin
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
  1. FDA Approved Drug Products: Adakveo Crizanlizumab-TMCA Intravenous Injection [Link]

Drug created at May 20, 2019 15:06 / Updated at February 21, 2021 18:55