Identification
NameMepolizumab
Accession NumberDB06612
TypeBiotech
GroupsApproved, Investigational
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.

Protein structureDb06612
Related Articles
Protein chemical formulaNot Available
Protein average weight149000.0 Da
SequencesNot Available
SynonymsNot Available
External IDs 240563 / SB-240563
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NucalaPowder, for solution144 mgSubcutaneousGlaxosmithkline Inc2016-03-14Not applicableCanada
NucalaInjection, powder, for solution100 mg/mLSubcutaneousGlaxosmithkline Inc2015-11-04Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BosatriaGlaxoSmithKline
Brand mixturesNot Available
Categories
UNII90Z2UF0E52
CAS number196078-29-2
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

Structured Indications
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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Interleukin-5Proteinyes
antagonist
HumanP05113 details
Related Articles
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 eliminationNot 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.

ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of Bcg can be decreased when used in combination with Mepolizumab.Investigational
BelimumabThe risk or severity of adverse effects can be increased when Mepolizumab is combined with Belimumab.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Mepolizumab.Approved
FingolimodMepolizumab may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe risk or severity of adverse effects can be increased when Mepolizumab is combined with G17DT.Investigational
INGN 201The risk or severity of adverse effects can be increased when Mepolizumab is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Mepolizumab is combined with INGN 225.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Mepolizumab is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Mepolizumab is combined with Natalizumab.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Mepolizumab.Approved, Investigational
RindopepimutThe risk or severity of adverse effects can be increased when Mepolizumab is combined with CDX-110.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Mepolizumab.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Mepolizumab.Approved
SRP 299The risk or severity of adverse effects can be increased when Mepolizumab is combined with SRP 299.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Mepolizumab.Approved, Investigational
TofacitinibMepolizumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Mepolizumab.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
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 ]
External Links
ATC CodesL04AC06 — Mepolizumab
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (3.56 MB)
MSDSDownload (86.4 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedOtherAsthma Bronchial1
1, 2CompletedTreatmentChurg-Strauss Syndrome (CSS) / Eosinophilic Gastroenteritis / Hypereosinophilic Syndromes / Oesophagitis, Eosinophilic1
1, 2Unknown StatusTreatmentAllergic granulomatous angiitis1
2Active Not RecruitingOtherAsthma Bronchial1
2CompletedTreatmentAllergic granulomatous angiitis1
2CompletedTreatmentAsthma Bronchial3
2CompletedTreatmentBullous Pemphigoid (BP)1
2CompletedTreatmentEosinophilic Oesophagitis in Adult Patients / Oesophagitis, Eosinophilic1
2CompletedTreatmentHypereosinophilia / Hypereosinophilic Syndromes1
2CompletedTreatmentOesophagitis, Eosinophilic1
2CompletedTreatmentPolyps, Nasal1
2RecruitingTreatmentModerate, refractory Atopic dermatitis1
3Active Not RecruitingTreatmentAsthma Bronchial2
3CompletedTreatmentAsthma Bronchial5
3CompletedTreatmentBronchitis / Chronic Airways Limitation / Chronic Obstructive Pulmonary Disease (COPD)1
3CompletedTreatmentChurg-Strauss Syndrome (CSS)1
3CompletedTreatmentPulmonary Disease, Chronic Obstructive2
3RecruitingTreatmentAsthma Bronchial3
3RecruitingTreatmentHypereosinophilic Syndromes1
3RecruitingTreatmentPolyps, Nasal1
3TerminatedTreatmentAsthma Bronchial1
3TerminatedTreatmentHypereosinophilic Syndromes1
3Unknown StatusPreventionAsthma Bronchial / Viral Infections1
4CompletedTreatmentAsthma Bronchial1
Not AvailableActive Not RecruitingNot AvailableAsthma Bronchial1
Not AvailableActive Not RecruitingBasic ScienceAsthma Bronchial1
Not AvailableAvailableNot AvailableHypereosinophilic Syndromes1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionSubcutaneous100 mg/mL
Powder, for solutionSubcutaneous144 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US2008134721 No2007-04-302027-04-30Us
Properties
StateSolid
Experimental PropertiesNot Available
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
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 August 17, 2016 12:24