Omalizumab

Identification

Summary

Omalizumab is a monoclonal anti-immunoglobulin E (IgE) antibody used to treat asthma, chronic idiopathic urticaria, chronic rhinosinusitis with nasal polyps, and IgE-mediated food allergy.

Brand Names
Xolair
Generic Name
Omalizumab
DrugBank Accession Number
DB00043
Background

Omalizumab is a recombinant DNA-derived humanized monoclonal antibody directed against human immunoglobulin E (IgE).7 IgE promotes the release of inflammatory mediators from mast cells and basophils during allergic and inflammatory reactions. By binding to IgE and neutralizing it, omalizumab reduces free IgE levels and prevents IgE from binding to its receptors on immune cells.1

Omalizumab was first approved in the US in 2003 3 and in Europe in 2005.7 It is used to treat a range of immune and inflammatory conditions, including allergies, urticaria, and asthma.3

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Protein Chemical Formula
Not Available
Protein Average Weight
149000.0 Da (approximate)
Sequences
Not Available
Synonyms
  • Omalizumab
  • RHUMAB-E25
External IDs
  • IGE25
  • RG-3648

Pharmacology

Indication

Omalizumab is indicated for: - the treatment of patients six years of age and older with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids.6,7 - add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adults with inadequate response to nasal corticosteroids.6,7 - the reduction of allergic reactions (Type I), including anaphylaxis, that may occur with accidental exposure to one or more foods in patients aged one year and older with IgE-mediated food allergy. Omalizumab is to be used in conjunction with food allergen avoidance.6 - the treatment of adults and adolescents 12 years of age and older with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1 antihistamine treatment.6

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofChronic idiopathic urticaria••••••••••••••••••••••• ••••••••••••••• •••••••• •• ••••••••••••• •••••••••
Management ofChronic rhinosinusitis phenotype with nasal polyps (crswnp)••••••••••••••••••••••••••• •••••••• •• ••••• •••••••••••••••
Management ofModerate asthma••••••••••••••••••••••• •••••• ••••••••••••••••• •••••••••••• •••••••••• •••• ••••••• •••••••••••••••
Management ofSevere asthma••••••••••••••••••••••• •••••• ••••••••••••••••• •••••••••••• •••••••••• •••• ••••••• •••••••••••••••
Prophylaxis ofType i hypersensitivity••••••••••••••• •••••••• •••• •••••••• •••••••••• ••••••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Omalizumab decreases free IgE levels in serum in a dose-dependent manner. Serum total IgE levels, accounting for bound and unbound IgE, increased after the first dose of omalizumab due to the formation of drug:IgE complexes, which have a slower elimination rate compared with free IgE. At 16 weeks after the first dose, average total IgE levels in serum were five-fold higher compared to pre-treatment levels in standard assays. Drug effects on IgE levels are reversible upon drug discontinuation, with no observed rebound in IgE levels after drug washout. Total IgE levels did not return to pre-treatment levels for up to one year after discontinuation of omalizumab.6

Mechanism of action

IgE antibodies have been implicated in several immune-mediated diseases, including allergic hypersensitivity reactions and asthma. IgE binds to the high-affinity IgE receptor Fc-epsilon-RI typically found on inflammatory cells such as eosinophils, mast cells, and basophils.1,3 IgE binding to Fc-epsilon-RI initiates a downstream cascade that releases pro-inflammatory mediators.1

Omalizumab is an IgE-neutralizing antibody: It selectively binds to the C-epsilon-3 locus of IgE, the domain at which IgE binds to Fc-epsilon-RI to mediate its actions. Omalizumab works to lower circulating free IgE levels and prevent IgE from interacting with Fc-epsilon-RI,3 which can also lead to the reduced expression of Fc-epsilon-RI.4

TargetActionsOrganism
AImmunoglobulin heavy constant epsilon
antibody
neutralizer
Humans
Absorption

After subcutaneous administration, omalizumab has an average absolute bioavailability of 62%. In adult and adolescent patients with asthma, omalizumab was absorbed slowly and the peak serum concentrations occurred after seven to eight days.6

The pharmacokinetics of omalizumab were 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. After repeated dosing from 75mg-300 mg every 4 weeks, trough serum concentrations of omalizumab increased proportionally with the dose.6

Volume of distribution

In patients with asthma, the apparent volume of distribution was 78 ± 32 mL/kg following subcutaneous administration.6

Protein binding

Not Available

Metabolism

Omalizumab is degraded in the reticuloendothelial system and endothelial cells.3

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 studies with mice and monkeys, omalizumab:IgE complexes were eliminated by interactions with Fc-gamma receptors within the RES at rates that were generally faster than IgG clearance.6

Half-life

In asthma patients, the serum elimination half-life averaged 26 days. In CSU patients, at steady state, based on population pharmacokinetics, omalizumab serum elimination half-life averaged 24 days.6

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. The apparent clearance averaged 2.4 ± 1.1 mL/kg/day in patients with asthma. The apparent clearance averaged 240 mL/day (corresponding to 3.0 mL/kg/day for an 80 kg patient).7

Adverse Effects
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Toxicity

The intravenous LD50 in monkeys is 200 mg/kg.8

Maximum tolerated dose of omalizumab has not been determined. Single intravenous doses up to 4000 mg have been administered to patients without evidence of dose-limiting toxicities. The highest cumulative dose administered to patients was 44,000 mg over a 20-week period and this dose did not result in any untoward acute effects. If an overdose is suspected, the patient should be monitored for any abnormal signs or symptoms. Medical treatment should be sought and instituted appropriately.7

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.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Omalizumab is combined with Abciximab.
AdalimumabThe risk or severity of adverse effects can be increased when Omalizumab is combined with Adalimumab.
AducanumabThe risk or severity of adverse effects can be increased when Omalizumab is combined with Aducanumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Omalizumab is combined with Alemtuzumab.
AlirocumabThe risk or severity of adverse effects can be increased when Omalizumab is combined with Alirocumab.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
XolairInjection, solution150 mgSubcutaneousNovartis Europharm Limited2020-12-16Not applicableEU flag
XolairInjection, solution75 mgSubcutaneousNovartis Europharm Limited2023-11-28Not applicableEU flag
XolairInjection, solution75 mgSubcutaneousNovartis Europharm Limited2020-12-16Not applicableEU flag
XolairInjection, solution300 mgSubcutaneousNovartis Europharm Limited2023-11-28Not applicableEU flag
XolairInjection, powder, for solution150 mgSubcutaneousNovartis Europharm Limited2020-12-16Not applicableEU flag

Categories

ATC Codes
R03DX05 — Omalizumab
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 and other mammals

Chemical Identifiers

UNII
2P471X1Z11
CAS number
242138-07-4

References

General References
  1. 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]
  2. 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]
  3. Kumar C, Zito PM: Omalizumab. . [Article]
  4. Okayama Y, Matsumoto H, Odajima H, Takahagi S, Hide M, Okubo K: Roles of omalizumab in various allergic diseases. Allergol Int. 2020 Apr;69(2):167-177. doi: 10.1016/j.alit.2020.01.004. Epub 2020 Feb 14. [Article]
  5. Pelaia C, Calabrese C, Terracciano R, de Blasio F, Vatrella A, Pelaia G: Omalizumab, the first available antibody for biological treatment of severe asthma: more than a decade of real-life effectiveness. Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618810192. doi: 10.1177/1753466618810192. [Article]
  6. FDA Approved Drug Products: XOLAIR (omalizumab) injection, for subcutaneous use (February 2024) [Link]
  7. EMA Approved Drug Products: Xolair (omalizumab) Subcutaneous Injection [Link]
  8. Genentech: XOLAIR (omalizumab) MSDS [Link]
UniProt
P01857
Genbank
J00228
PubChem Substance
46507002
RxNav
302379
ChEMBL
CHEMBL1201589
Therapeutic Targets Database
DAP000387
PharmGKB
PA164752253
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Omalizumab

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
4Active Not RecruitingTreatmentAsthma / Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)1somestatusstop reasonjust information to hide
4CompletedNot AvailableAtopic Dermatitis1somestatusstop reasonjust information to hide
4CompletedBasic ScienceAsthma1somestatusstop reasonjust information to hide
4CompletedDiagnosticAsthma, Allergic1somestatusstop reasonjust information to hide
4CompletedTreatmentAllergic Rhinitis (AR) / Asthma / Atopic Dermatitis1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Genentech Inc.
  • Novartis AG
Dosage Forms
FormRouteStrength
InjectionSubcutaneous150 MG
Injection, powder, for solutionSubcutaneous150 MG
Injection, powder, for solutionSubcutaneous75 MG
Injection, solutionParenteral; Subcutaneous150 MG
Injection, solutionParenteral; Subcutaneous300 mg
Injection, solutionParenteral; Subcutaneous75 MG
Injection, solutionSubcutaneous150 mg/1.2mL
Injection, solutionSubcutaneous300 mg/2mL
Injection, solutionSubcutaneous300 mg
Injection, solutionSubcutaneous75 mg
Powder150 mg/1vial
Powder, for solutionSubcutaneous150 mg / vial
SolutionSubcutaneous150 mg / 1 mL
SolutionSubcutaneous150 mg / mL
SolutionSubcutaneous300 mg / 2 mL
SolutionSubcutaneous75 mg / 0.5 mL
SolutionSubcutaneous75.000 mg
SolutionSubcutaneous150 mg
SolutionSubcutaneous75 mg
Injection, solutionSubcutaneous150 mg
Injection, solutionSubcutaneous150 mg/ml
Injection, powder, lyophilized, for solutionSubcutaneous150 mg
SolutionSubcutaneous150 mg/ml
Injection, powder, lyophilized, for solutionSubcutaneous75 mg
SolutionSubcutaneous75 mg/0.5ml
Injection, solutionSubcutaneous150 mg/1mL
Injection, solutionSubcutaneous75 mg/0.5mL
Injection, solutionSubcutaneous150 mg/1.0mL
Prices
Unit descriptionCostUnit
Xolair 150 mg vial715.42USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2113813No2005-04-122012-08-14Canada flag
CA1340233No1998-12-152015-12-15Canada flag

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
Neutralizer
General Function
Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268).
Specific Function
Antigen binding
Gene Name
IGHE
Uniprot ID
P01854
Uniprot Name
Immunoglobulin heavy constant epsilon
Molecular Weight
47018.665 Da
References
  1. Pelaia C, Calabrese C, Terracciano R, de Blasio F, Vatrella A, Pelaia G: Omalizumab, the first available antibody for biological treatment of severe asthma: more than a decade of real-life effectiveness. Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618810192. doi: 10.1177/1753466618810192. [Article]
  2. 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]
  3. FDA Approved Drug Products: XOLAIR (omalizumab) injection, for subcutaneous use (February 2024) [Link]

Drug created at June 13, 2005 13:24 / Updated at April 27, 2024 13:27