Omalizumab
Identification
- Summary
Omalizumab is a monoclonal anti-immunoglobulin E antibody used in the treatment of severe asthma and chronic idiopathic urticaria.
- Brand Names
- Xolair
- Generic Name
- Omalizumab
- DrugBank Accession Number
- DB00043
- Background
Omalizumab, manufactured by Genentech, was first FDA approved in 2003 to treat adults and children 12 years of age and older with moderate to severe persistent allergic asthma which is not controlled by inhaled steroids 6. Since its U.S. approval, more than 200,000 patients older than 12 with allergic asthma have been treated 6. In September 2018, a new prefilled syringe formulation of this drug was approved by the FDA 7.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6450H9916N1714O2023S38
- Protein Average Weight
- 149000.0 Da
- Sequences
>Omalizumab heavy chain EVQLVESGGGLVQPGGSLRLSCAVSGYSITSGYSWNWIRQAPGKGLEWVASITYDGSTNY ADSVKGRFTISRDDSKNTFYLQMNSLRAEDTAVYYCARGSHYFGHWHFAVWGQGTLVTVS SGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK
>Omalizumab light chain DIQLTQSPSSLSASVGDRVTITCRASQSVDYDGDSYMNWYQQKPGKAPKLLIYAASYLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHEDPYTFGQGTKVEIKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
Download FASTA Format- Synonyms
- Omalizumab
Pharmacology
- Indication
This drug is an anti-IgE antibody indicated for:
Moderate to severe persistent asthma in patients 6 years of age and older with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids Label
Chronic idiopathic urticaria in adults and adolescents 12 years of age and older who remain symptomatic despite H1 antihistamine treatment Label
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Chronic idiopathic urticaria •••••••••••• ••••••••••• ••••••• •• ••••••••••••• ••••••••• Management of Moderate asthma •••••••••••• •••••••• •••••••••••• •••••••••• •••• ••••••• ••••••••••••••• •••••••••• •••••••• Management of Severe asthma •••••••••••• •••••••• •••••••••••• •••••••••• •••• ••••••• ••••••••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Omalizumab is a recombinant, humanized, monoclonal antibody against human immunoglobulin E (IgE) which treats the symptoms of asthma and chronic idiopathic urticaria by limiting the allergic response Label, 3. It inhibits the binding of IgE to receptors on mast cells and basophils, blocking the IgE-mediated secretion of inflammatory mediators from these cells 1.
Mast cell activation and the release of mediators, in response to allergen exposure and IgE, results in a cascade of events. This cascade culminates in the activation of B-lymphocytes, T-lymphocytes, eosinophils, fibroblasts, smooth muscle cells, and the endothelium. This cellular interaction, as well as the release of cytokines, chemokines and growth factors and inflammatory remodeling of the airway results in chronic asthma 2.
After 4 weeks of use of this medication in patients with chronic urticaria, it was found that rescue medication use was reduced significantly and quality of life improved 4.
- Mechanism of action
When an environmental allergen first enters the body, is taken up by antigen-presenting cells (APCs). It is then processed, and presented to T and B immune cells. This is followed by the activation of B-lymphocyte and production of allergen-specific IgE. This IgE is then released by plasma cells (converted B lymphocytes) and is therefore available to bind to IgE receptors on several other cells 3.
IgE binds to high-affinity (Fc€RI) and low-affinity (Fc€RII) receptors on multiple cells of the immune system. Following subsequent antigen exposure, cross-linking of the antigen occurs by several Fc€RI-bound IgE molecules on the surface of both basophils and mast cells. This leads to the activation of mast cells and histamine release, producing a wheal and other symptoms of urticaria 3.
The following are explanations of the mechanism of action for both indications of this drug:
Asthma
Omalizumab inhibits the binding of IgE to the high-affinity IgE receptor (FcεRI) on the surface of both mast cells and basophils. The reduction in surface-bound IgE on FcεRI-bearing cells limits the degree of release of mediators of the typical allergic response. Treatment with omalizumab also reduces the number of FcεRI receptors on basophils in atopic patients Label.
Omalizumab binds to free IgE with a higher affinity than IgE itself binds to the high-affinity Fc€RI receptors found on basophils. Therefore, it decreases the availability of free IgE for binding 3. Omalizumab by itself does not bind to the Fc€RI receptors, nor does the drug bind to receptor-bound IgE. These binding characteristics allow omalizumab to neutralize the typical IgE-mediated responses without causing the degranulation of basophils or cross-linking with basophil-bound IgE 3.
Chronic Idiopathic Urticaria Omalizumab binds to IgE and decreases free IgE levels. Subsequently, IgE receptors (FcεRI) on cells are down-regulated. The mechanism by which these effects of omalizumab result in an improvement of CIU symptoms is unclearLabel.
Target Actions Organism AHigh affinity immunoglobulin epsilon receptor subunit alpha inhibitorHumans AHigh affinity immunoglobulin epsilon receptor subunit beta inhibitorHumans - Absorption
After subcutaneous administration in pharmacokinetic studies, omalizumab was absorbed with a mean absolute bioavailability of 62% Label. After the administration of a single subcutanous dose in adult and adolescent patients with asthma, omalizumab was absorbed slowly. The peak serum concentrations peaked after an average of 7-8 days. In patients with CIU, the peak serum concentration was reached at a similar time after a single SC dose. The pharmacokinetics of omalizumab was linear at doses which were higher than 0.5 mg/kg. In patients with asthma, after several doses of omalizumab, areas under the serum concentration-time curve from Day 0 to Day 14 at steady state were up to 6-fold of those after one dose. In patients with CIU, omalizumab showed linear pharmacokinetics in the dose range of 75 mg to 600 mg administered as a single subcutaneous dose. After repeated dosing from 75mg-300 mg every 4 weeks, trough serum concentrations of omalizumab increased proportionally with the dose Label.
- Volume of distribution
The apparent volume of distribution of omalizumab in patients with asthma after subcutaneous administration was 78 ± 32 mL/kg. In patients with CIU, the distribution of omalizumab was similar to that in asthmatic patients Label.
- Protein binding
Monoclonal antibodies are usually not required to have protein binding studies.
- Metabolism
Monoclonal antibodies, in general, are believed to be internalized in endothelial cells bound to the Fc receptor and rescued from metabolism by recycling. At a later time, they are degraded in the reticuloendothelial system to smaller peptides and amino acids, which can then be used for de-novo protein synthesis 5. Several factors may influence this process, however. These include factors related to the target antigen, antibody, and patient 5.
The metabolism of omalizumab is determined by its IgG1 framework, and by its specific binding to IgE. The elimination of omalizumab is dose-dependent. The reticuloendothelial system and the liver are two sites of elimination for IgG (including degradation in the liver reticuloendothelial system and endothelial cells) 9, 5. The omalizumab:IgE complexes are thought to be to cleared via interactions with Fc- gamma-Rs (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) at rates that are more rapid than that of IgG clearance. The relative clearance of free omalizumab, free IgE, and complexes is summarized as: free IgE clearance > > omalizumab:IgE clearance > omalizumab clearance 9.
- Route of elimination
Liver elimination of IgG includes degradation in the liver reticuloendothelial system (RES) and endothelial cells. Intact IgG was also shown to be excreted in bile, in pharmacokinetic studies Label.
- Half-life
In chronic idiopathic urticaria (CIU) patients, at steady state, based on population pharmacokinetics, omalizumab serum elimination half-life averaged 24 days Label.
In asthmatic patients omalizumab serum elimination half-life averaged 26 days Label.
- Clearance
In pharmacokinetic studies, the clearance of omalizumab involved IgG clearance as well as clearance by specific binding and complex formation with its target ligand, IgE Label, 9.
The apparent clearance averaging 2.4 ± 1.1 mL/kg/day was measured in asthmatic patients Label.
In chronic idiopathic urticaria (CIU) patients, at steady state, based on population pharmacokinetics, omalizumab apparent clearance averaged 240 mL/day (corresponding to 3.0 mL/kg/day for an 80 kg patient)Label.
- Adverse Effects
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- Toxicity
Anaphylaxis
Anaphylaxis may occur rarely with this agent, either after the first dose or multiple doses Label, 2. Anaphylaxis presenting clinically as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue, has been reported during and after this use of this drug. Therefore, close clinical monitoring should be performed during and shortly after administration Label.
Maximum Dosage
The maximum tolerated dosage of omalizumab has not yet been determined. Single intravenous (IV) doses of up to 4000 mg have been administered to patients without evidence of dose-limiting toxicity. The highest cumulative dose administered to patients was 44,000 mg over a 20 week time period, which was not associated with any toxicities Label.
The use in Pregnancy
The data with omalizumab use in pregnant women are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as omalizumab, are transported across the placenta in a linear fashion as a pregnancy progresses; therefore, potential effects on a fetus are likely to be greater in frequency during the second and third trimesters Label.
In women with inadequately or moderately controlled asthma, the current evidence suggests that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small fetal size Label.
The use During Breastfeeding
There is no information regarding the presence of omalizumab in human milk, the effects on the breastfed infant, or the effects on milk production Label. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for omalizumab and any potential adverse effects on the breastfed child from omalizumab or from the underlying maternal condition Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Omalizumab is combined with Abciximab. Adalimumab The risk or severity of adverse effects can be increased when Omalizumab is combined with Adalimumab. Aducanumab The risk or severity of adverse effects can be increased when Omalizumab is combined with Aducanumab. Alemtuzumab The risk or severity of adverse effects can be increased when Omalizumab is combined with Alemtuzumab. Alirocumab The risk or severity of adverse effects can be increased when Omalizumab is combined with Alirocumab. - 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 Xolair Solution 150 mg / mL Subcutaneous Novartis 2017-07-06 Not applicable Canada Xolair Injection, solution 300 mg Subcutaneous Novartis Europharm Limited 2023-11-28 Not applicable EU Xolair Injection, solution 150 mg Subcutaneous Novartis Europharm Limited 2023-11-28 Not applicable EU Xolair Injection, solution 300 mg Subcutaneous Novartis Europharm Limited 2023-11-28 Not applicable EU Xolair Injection, solution 75 mg Subcutaneous Novartis Europharm Limited 2023-11-28 Not applicable EU
Categories
- ATC Codes
- R03DX05 — Omalizumab
- Drug Categories
- Agents to Treat Airway Disease
- Amino Acids, Peptides, and Proteins
- Anti-Allergic Agents
- Anti-Asthmatic Agents
- Anti-IgE
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Blood Proteins
- Decreased IgE Activity
- Globulins
- IgE-directed Antibody Interactions
- Immunoglobulins
- Immunoproteins
- Proteins
- Respiratory Agents, Miscellaneous
- Respiratory System Agents
- Serum Globulins
- 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 and other mammals
Chemical Identifiers
- UNII
- 2P471X1Z11
- CAS number
- 242138-07-4
References
- General References
- Jensen RK, Plum M, Tjerrild L, Jakob T, Spillner E, Andersen GR: Structure of the omalizumab Fab. Acta Crystallogr F Struct Biol Commun. 2015 Apr;71(Pt 4):419-26. doi: 10.1107/S2053230X15004100. Epub 2015 Mar 20. [Article]
- Miller CW, Krishnaswamy N, Johnston C, Krishnaswamy G: Severe asthma and the omalizumab option. Clin Mol Allergy. 2008 May 20;6:4. doi: 10.1186/1476-7961-6-4. [Article]
- Godse K, Mehta A, Patil S, Gautam M, Nadkarni N: Omalizumab-A Review. Indian J Dermatol. 2015 Jul-Aug;60(4):381-4. doi: 10.4103/0019-5154.160490. [Article]
- Kaplan AP, Joseph K, Maykut RJ, Geba GP, Zeldin RK: Treatment of chronic autoimmune urticaria with omalizumab. J Allergy Clin Immunol. 2008 Sep;122(3):569-73. doi: 10.1016/j.jaci.2008.07.006. [Article]
- 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]
- FDA Approves Genentech’s Xolair® (omalizumab) for Allergic Asthma in Children [Link]
- FDA Approves Genentech's Xolair (omalizumab) Prefilled Syringe Formulation [Link]
- Omalizumab properties, THPdb Database [Link]
- Xolair EMA label [File]
- External Links
- UniProt
- P01857
- Genbank
- J00228
- PubChem Substance
- 46507002
- 302379
- ChEMBL
- CHEMBL1201589
- Therapeutic Targets Database
- DAP000387
- PharmGKB
- PA164752253
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Omalizumab
- MSDS
- Download (582 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Not Available Atopic Dermatitis 1 4 Completed Basic Science Asthma 1 4 Completed Diagnostic Asthma, Allergic 1 4 Completed Treatment Allergic Rhinitis (AR) / Asthma / Atopic Dermatitis 1 4 Completed Treatment Aspirin Sensitivity 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Genentech Inc.
- Novartis AG
- Dosage Forms
Form Route Strength Injection Subcutaneous 150 MG Injection, powder, for solution Subcutaneous 150 MG Injection, powder, for solution Subcutaneous 75 MG Injection, solution Parenteral; Subcutaneous 150 MG Injection, solution Parenteral; Subcutaneous 75 MG Injection, solution Subcutaneous 150 mg/1.2mL Injection, solution Subcutaneous 300 mg Injection, solution Subcutaneous 300 mg/2mL Injection, solution Subcutaneous 75 mg Powder 150 mg/1vial Powder, for solution Subcutaneous 150 mg / vial Solution Subcutaneous 150 mg / mL Solution Subcutaneous 75 mg / 0.5 mL Solution Subcutaneous 75.000 mg Solution Subcutaneous 150 mg Solution Subcutaneous 75 mg Injection, solution Subcutaneous 150 mg Injection, solution Subcutaneous 150 mg/ml Injection, powder, lyophilized, for solution Subcutaneous 150 mg Injection, powder, for solution Subcutaneous Injection, powder, lyophilized, for solution Subcutaneous 75 mg Injection, solution Subcutaneous 150 mg/1mL Injection, solution Subcutaneous 75 mg/0.5mL Injection, solution Subcutaneous 150 mg/1.0mL - Prices
Unit description Cost Unit Xolair 150 mg vial 715.42USD vial DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2113813 No 2005-04-12 2012-08-14 Canada CA1340233 No 1998-12-15 2015-12-15 Canada
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 61 °C (FAB fragment) http://crdd.osdd.net/raghava/thpdb/display_thppid_sub.php?details=Th1038 boiling point (°C) Fab and Fc domains denaturates at 60 and 70 ºC respectively Arnoldus W. et al. (2000). Biophysical Journal. Vol 78. 394-404 hydrophobicity -0.432 Not Available isoelectric point 6.6 - 7.2 Jin, et al. Electrophoresis. Sep;23(19):3385-91. (2002).
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Ige receptor activity
- Specific Function
- Binds to the Fc region of immunoglobulins epsilon. High affinity receptor. Responsible for initiating the allergic response. Binding of allergen to receptor-bound IgE leads to cell activation and t...
- Gene Name
- FCER1A
- Uniprot ID
- P12319
- Uniprot Name
- High affinity immunoglobulin epsilon receptor subunit alpha
- Molecular Weight
- 29595.67 Da
References
- Beck LA, Marcotte GV, MacGlashan D, Togias A, Saini S: Omalizumab-induced reductions in mast cell Fce psilon RI expression and function. J Allergy Clin Immunol. 2004 Sep;114(3):527-30. [Article]
- Mirkina I, Schweighoffer T, Kricek F: Inhibition of human cord blood-derived mast cell responses by anti-Fc epsilon RI mAb 15/1 versus anti-IgE Omalizumab. Immunol Lett. 2007 Apr 15;109(2):120-8. Epub 2007 Mar 1. [Article]
- Godse K, Mehta A, Patil S, Gautam M, Nadkarni N: Omalizumab-A Review. Indian J Dermatol. 2015 Jul-Aug;60(4):381-4. doi: 10.4103/0019-5154.160490. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Ige receptor activity
- Specific Function
- High affinity receptor that binds to the Fc region of immunoglobulins epsilon. Aggregation of FCER1 by multivalent antigens is required for the full mast cell response, including the release of pre...
- Gene Name
- MS4A2
- Uniprot ID
- Q01362
- Uniprot Name
- High affinity immunoglobulin epsilon receptor subunit beta
- Molecular Weight
- 26533.365 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- DuBuske LM: IgE, allergic diseases, and omalizumab. Curr Pharm Des. 2006;12(30):3929-44. [Article]
- Raunio H, Rautio A, Gullsten H, Pelkonen O: Polymorphisms of CYP2A6 and its practical consequences. Br J Clin Pharmacol. 2001 Oct;52(4):357-63. [Article]
Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:41