Mepolizumab

Identification

Name
Mepolizumab
Accession Number
DB06612
Description

Mepolizumab is a humanized IL-5 antagonist monoclonal antibody produced by recombinant DNA technology in Chinese hamster ovary cells. It has a molecular weight of approximately 149 kDa. It was approved by the FDA in November, 2015 for the treatment of asthma under the brand name Nucala (marketed by GlaxoSmithKline). Mepolizumab has been investigated in the treatment of severe nasal polyposis, among numerous other conditions.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Db06612
Protein Chemical Formula
Not Available
Protein Average Weight
149000.0 Da
Sequences
Not Available
Synonyms
  • Mepolizumab
External IDs
  • SB 240563
  • SB-240563

Pharmacology

Indication

Mepolizumab is indicated for add-on maintenance treatment of severe eosinophilic asthma, as identified by blood eosinophils greater than or equal to 150 cells/μl at initiation of treatment or blood eosinophils greater than or equal to 300 cells/μl in the past 12 months, in patients aged 12 years and older. Mepolizumab has been shown to reduce exacerbations of asthma in patients with an exacerbation history

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

The pharmacodynamic response (blood eosinophil reduction) following repeat doses of mepolizumab administered subcutaneously or intravenously was evaluated in subjects with asthma and blood eosinophil levels greater than 200 cells/mcL. Subjects received 1 of 4 mepolizumab treatments (administered every 28 days for a total of 3 doses): 12.5 mg SC, 125 mg SC, 250 mg SC, or 75 mg IV. Sixty-six (66) of the 70 randomized subjects completed the trial. Compared with baseline levels, blood eosinophils decreased in a dose-dependent manner. A reduction in blood eosinophil levels was observed in all treatment groups by Day 3. On Day 84 (4 weeks post-last dose), the observed geometric mean reduction from baseline in blood eosinophils was 64%, 78%, 84%, and 90% in the 12.5-mg SC, 75-mg IV, 125-mg SC, and 250-mg SC treatment groups, respectively. The model-predicted SC doses providing 50% and 90% of maximal reduction of blood eosinophils at Day 84 were estimated to be 11 and 99 mg, respectively. These results, along with the clinical efficacy data from the dose-ranging exacerbation trial (Trial 1) supported the evaluation of mepolizumab 75 mg IV and 100 mg SC in the confirmatory trials [see Clinical Studies (14)]. Following SC administration of mepolizumab 100 mg every 4 weeks for 32 weeks (Trial 2), blood eosinophils were reduced to a geometric mean count of 40 cells/mcL, which corresponds to a geometric mean reduction of 84% compared with placebo. This magnitude of reduction was observed within 4 weeks of treatment and was maintained throughout the treatment period.

Mechanism of action

Mepolizumab is an interleukin-5 antagonist (IgG1 kappa). IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Mepolizumab binds to IL-5 with a dissociation constant of 100 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface. Inflammation is an important component in the pathogenesis of asthma. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Mepolizumab, by inhibiting IL-5 signaling, reduces the production and survival of eosinophils; however, the mechanism of mepolizumab action in asthma has not been definitively established.

TargetActionsOrganism
AInterleukin-5
antagonist
Humans
Absorption

Following 100-mg SC administration in the upper arm of subjects with asthma, the bioavailability of mepolizumab was estimated to be approximately 80%. Following repeat SC administration once every 4 weeks, there was approximately a 2-fold accumulation at steady state.

Volume of distribution

The population central volume of distribution of mepolizumab in patients with asthma is estimated to be 3.6 L for a 70-kg individual.

Protein binding

Mepolizumab binds to IL-5 with a dissociation constant of 100 pM.

Metabolism

Mepolizumab is a humanized IgG1 monoclonal antibody that is degraded by proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue.

Route of elimination
Not Available
Half-life

The mean terminal half-life (t1/2) ranged from 16 to 22 days.

Clearance

The population apparent systemic clearance of mepolizumab in patients with asthma is estimated to be 0.28 L/day for a 70-kg individual.

Adverse Effects
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
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
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Mepolizumab.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Mepolizumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Mepolizumab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Mepolizumab.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Mepolizumab.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Mepolizumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Mepolizumab.
AlirocumabThe risk or severity of adverse effects can be increased when Mepolizumab is combined with Alirocumab.
AltretamineThe risk or severity of adverse effects can be increased when Altretamine is combined with Mepolizumab.
AmsacrineThe risk or severity of adverse effects can be increased when Amsacrine is combined with Mepolizumab.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

International/Other Brands
Bosatria (GlaxoSmithKline)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NucalaInjection, solution100 mg/1mLSubcutaneousGlaxoSmithKline LLC2019-06-06Not applicableUS flag
NucalaSolution100 mgSubcutaneousGlaxosmithkline Inc2019-12-10Not applicableCanada flag
NucalaInjection, powder, for solution100 mg/1mLSubcutaneousGlaxoSmithKline LLC2015-11-04Not applicableUS flag
NucalaSolution100 mgSubcutaneousGlaxosmithkline Inc2019-12-10Not applicableCanada flag
NucalaInjection, powder, for solution100 mg/1mLSubcutaneousGlaxoSmithKline Manufacturing SpA2015-11-042017-12-12US flag
NucalaPowder, for solutionSubcutaneousGlaxosmithkline Inc2016-03-14Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
R03DX09 — Mepolizumab
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

Chemical Identifiers

UNII
90Z2UF0E52
CAS number
196078-29-2

References

General References
  1. Garrett JK, Jameson SC, Thomson B, Collins MH, Wagoner LE, Freese DK, Beck LA, Boyce JA, Filipovich AH, Villanueva JM, Sutton SA, Assa'ad AH, Rothenberg ME: Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol. 2004 Jan;113(1):115-9. Epub 2003 Dec 12. [PubMed:14699394]
KEGG Drug
D04923
PubChem Substance
347910353
RxNav
1720597
Drugs.com
Drugs.com Drug Page
Wikipedia
Mepolizumab
AHFS Codes
  • 92:44.00 — Immunosuppressive Agents
FDA label
Download (3.56 MB)
MSDS
Download (86.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAsthma2
4Not Yet RecruitingTreatmentAsthma1
4RecruitingTreatmentEosinophilic Asthma1
4RecruitingTreatmentSevere Asthma1
3Active Not RecruitingTreatmentAllergic granulomatous angiitis / Churg-Strauss Syndrome1
3CompletedTreatmentAllergic granulomatous angiitis / Churg-Strauss Syndrome1
3CompletedTreatmentAsthma10
3CompletedTreatmentBronchitis / Chronic Airways Limitation / Chronic Obstructive Pulmonary Disease (COPD)1
3CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)2
3CompletedTreatmentHypereosinophilia / Hypereosinophilic Syndromes1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionCutaneous; Parenteral100 MG
Injection, powder, for solutionSubcutaneous100 mg/1mL
Injection, solutionCutaneous100 MG
Injection, solutionSubcutaneous100 mg/1mL
Powder, for solutionSubcutaneous
SolutionSubcutaneous100 mg
Injection, powder, lyophilized, for solutionSubcutaneous100 mg
Injection, powder, for solutionSubcutaneous100 mg
Powder
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US20100086547No2007-04-302027-04-30US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Interleukin-5 receptor binding
Specific Function
Factor that induces terminal differentiation of late-developing B-cells to immunoglobulin secreting cells.
Gene Name
IL5
Uniprot ID
P05113
Uniprot Name
Interleukin-5
Molecular Weight
15237.695 Da
References
  1. Basavaraju KP, Wong T: Eosinophilic oesophagitis: a common cause of dysphagia in young adults? Int J Clin Pract. 2008 Jul;62(7):1096-107. doi: 10.1111/j.1742-1241.2008.01782.x. [PubMed:18564273]
  2. Garrett JK, Jameson SC, Thomson B, Collins MH, Wagoner LE, Freese DK, Beck LA, Boyce JA, Filipovich AH, Villanueva JM, Sutton SA, Assa'ad AH, Rothenberg ME: Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol. 2004 Jan;113(1):115-9. Epub 2003 Dec 12. [PubMed:14699394]

Drug created on March 19, 2008 10:41 / Updated on September 24, 2020 02:08

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