Mepolizumab: Difference between revisions

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| verifiedrevid = 462248575
| verifiedrevid = 462248575
| image =
| image =

<!-- Monoclonal antibody data -->
<!-- Monoclonal antibody data -->
| type = mab
| type = mab
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| source = zu/o
| source = zu/o
| target = [[Interleukin 5|IL-5]]
| target = [[Interleukin 5|IL-5]]

<!-- Clinical data -->
<!-- Clinical data -->
| pronounce =
⚫
| Drugs.com = {{Drugs.com|parent|nucala}}
| tradename = Nucala
| tradename = Nucala
⚫
| Drugs.com = {{Drugs.com|monograph|mepolizumab}}
| pregnancy_AU =
| MedlinePlus = a615058
| pregnancy_US =
| licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) -->
⚫
| pregnancy_category =
| licence_EU = yes
| licence_EU = yes
| DailyMedID = Mepolizumab
⚫
| legal_AU =
| licence_US = <!-- FDA may use generic or brand name (generic name preferred) -->
| legal_CA =
| legal_UK =
| pregnancy_AU = B1
| pregnancy_AU_comment =
⚫
| legal_US = Rx-only
| legal_status =
| pregnancy_US = N
| pregnancy_US_comment =
⚫
| pregnancy_category=
| dependency_liability =
| addiction_liability =
| routes_of_administration = [[Subcutaneous injection]]
| routes_of_administration = [[Subcutaneous injection]]
⚫
| ATC_prefix = R03
⚫
| ATC_suffix = DX09

⚫
<!-- Legal status -->
⚫
| legal_AU = S4
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment =
⚫
| legal_US = Rx-only
| legal_US_comment =
| legal_EU =
| legal_EU_comment =
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
<!-- Pharmacokinetic data -->
| bioavailability = 80% (estimate)
| bioavailability = 80% (estimate)
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| elimination_half-life = 20 (16–22) days
| elimination_half-life = 20 (16–22) days
| excretion =
| excretion =

<!-- Identifiers -->
<!-- Identifiers -->
⚫
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = None
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 196078-29-2
| CAS_number = 196078-29-2
| CAS_supplemental =
⚫
| ATC_prefix = R03
| PubChem =
⚫
| ATC_suffix = DX09
| IUPHAR_ligand =
| PubChemSubstance = 47206675
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB06612
| DrugBank = DB06612
⚫
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
⚫
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D04923
| ChemSpiderID = None
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 90Z2UF0E52
| UNII = 90Z2UF0E52
⚫
| KEGG_Ref = {{keggcite|correct|kegg}}
⚫
<!-- Chemical data -->
| KEGG = D04923
⚫
| chemical_formula =
| ChEBI_Ref =
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| molecular_weight = ~149 kg/mol
| ChEBI =
| ChEMBL_Ref =
| ChEMBL =
| NIAID_ChemDB =
| PDB_ligand =
| synonyms =

<!-- Chemical and physical data -->
| IUPAC_name =
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| chemical_formula =
| C= | H= | Ag= | Al= | As= | Au= | B= | Bi= | Br= | Ca= | Cl= | Co= | F= | Fe= | Gd= | I=
| K= | Li= | Mg= | Mn= | N= | Na= | O= | P= | Pt= | S= | Sb= | Se= | Sr= | Tc= | Zn= | charge=
⚫
| molecular_weight = 149 000
| SMILES =
| StdInChI =
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}}

'''Mepolizumab''' (trade name '''Nucala''') is a [[humanized antibody|humanized]] [[monoclonal antibody]] used for the treatment of severe [[eosinophilic asthma]]. It recognizes and blocks [[interleukin-5]] (IL-5), a signalling protein of the immune system.
'''Mepolizumab''', sold under the brand name '''Nucala''', is a [[humanized antibody|humanized]] [[monoclonal antibody]] used for the treatment of severe [[eosinophilic asthma]]. It recognizes and blocks [[interleukin-5]] (IL-5), a signalling protein of the immune system.


==Medical uses==
==Medical uses==
Mepolizumab is approved by the [[U.S. Food and Drug Administration]] (FDA) for the maintenance treatment of severe asthma in patients aged 6 years<ref>{{Cite journal|date=2020-01-30|title=FDA approves severe eosinophilic asthma treatment for children ages 6-11|url=https://www.aappublications.org/news/2019/09/13/mepolizumab091319|journal=AAP News|language=en}}</ref> or older and with an eosinophilic phenotype in combination with other medicines used to treat asthma.<ref name="FDA">{{cite news|title=FDA approves Nucala to treat severe asthma |publisher=FDA|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm471031.htm |date=4 Nov 2016}}</ref>
Mepolizumab is approved by the U.S. [[Food and Drug Administration]] (FDA) for the maintenance treatment of severe asthma in patients aged 6 years<ref>{{Cite journal|date=2020-01-30|title=FDA approves severe eosinophilic asthma treatment for children ages 6-11|url=https://www.aappublications.org/news/2019/09/13/mepolizumab091319|journal=AAP News|language=en}}</ref> or older and with an eosinophilic phenotype in combination with other medicines used to treat asthma.<ref name="FDA">{{cite press release |title=FDA approves Nucala to treat severe asthma |publisher=U.S. [[Food and Drug Administration]] (FDA)|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm471031.htm |date=4 November 2016}}</ref>
In Europe it is approved as an add-on treatment for severe refractory eosinophilic asthma in adult patients.<ref name="EPAR-summary">{{cite web|publisher=European Medicines Agency| title=Nucala EPAR Summary for the public |url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/003860/WC500198039.pdf|date=December 2015}}</ref>
In Europe it is approved as an add-on treatment for severe refractory eosinophilic asthma in adult patients.<ref name="EPAR-summary">{{cite web|publisher=European Medicines Agency| title=Nucala EPAR Summary for the public |url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/003860/WC500198039.pdf|date=December 2015}}</ref>


In studies, mepolizumab cut the necessity for hospitalisation due to asthma [[exacerbation]]s in half, as compared to [[placebo]].<ref>{{cite journal | vauthors = Yancey SW, Ortega HG, Keene ON, Mayer B, Gunsoy NB, Brightling CE, Bleecker ER, Haldar P, Pavord ID | display-authors = 6 | title = Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma | journal = The Journal of Allergy and Clinical Immunology | volume = 139 | issue = 4 | pages = 1167–1175.e2 | date = April 2017 | pmid = 27726946 | doi = 10.1016/j.jaci.2016.08.008 | url = http://www.jacionline.org/article/S0091-6749(16)30891-0/fulltext | doi-access = free }}</ref>
In studies, mepolizumab cut the necessity for hospitalisation due to asthma [[exacerbation]]s in half, as compared to [[placebo]].<ref>{{cite journal | vauthors = Yancey SW, Ortega HG, Keene ON, Mayer B, Gunsoy NB, Brightling CE, Bleecker ER, Haldar P, Pavord ID | display-authors = 6 | title = Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma | journal = The Journal of Allergy and Clinical Immunology | volume = 139 | issue = 4 | pages = 1167–1175.e2 | date = April 2017 | pmid = 27726946 | doi = 10.1016/j.jaci.2016.08.008 | url = http://www.jacionline.org/article/S0091-6749(16)30891-0/fulltext | doi-access = free }}</ref>


In December of 2017 the [[Food and Drug Administration|U.S. Food and Drug Administration]] expanded mepolizumab's use to treat adult patients with [[eosinophilic granulomatosis with polyangiitis]] (EGPA), which is a rare autoimmune condition that can cause [[vasculitis]].<ref>{{Cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm588594.htm|title=Press Announcements - FDA approves first drug for Eosinophilic Granulomatosis with Polyangiitis, a rare disease formerly known as the Churg-Strauss Syndrome|last=Commissioner|first=Office of the|website=www.fda.gov|language=en|access-date=2017-12-13}}</ref>
In December 2017, the FDA expanded mepolizumab's indication to treat adults with [[eosinophilic granulomatosis with polyangiitis]] (EGPA), which is a rare autoimmune condition that can cause [[vasculitis]].<ref>{{Cite press release |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm588594.htm|title=FDA approves first drug for Eosinophilic Granulomatosis with Polyangiitis, a rare disease formerly known as the Churg-Strauss Syndrome|website=U.S. [[Food and Drug Administration]] (FDA)|access-date=2017-12-13}}</ref>


==Side effects==
==Side effects==
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== References ==
== References ==
{{Reflist}}
{{Reflist}}

== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/mepolizumab | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Mepolizumab }}


{{Monoclonals for immune system}}
{{Monoclonals for immune system}}
{{Interleukin receptor modulators}}
{{Interleukin receptor modulators}}
{{Portal bar | Pharmacy and pharmacology | Medicine}}


[[Category:Antiasthmatic drugs]]
[[Category:Antiasthmatic drugs]]
[[Category:Immunosuppressants]]
[[Category:Immunosuppressants]]
[[Category:Monoclonal antibodies]]
[[Category:Monoclonal antibodies]]
[[Category:Orphan drugs]]

Revision as of 05:26, 19 July 2020

Mepolizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from mouse)
TargetIL-5
Clinical data
Trade namesNucala
AHFS/Drugs.comMonograph
MedlinePlusa615058
License data
Pregnancy
category
  • AU: B1
Routes of
administration		Subcutaneous injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability80% (estimate)
Protein bindingNone
MetabolismProteolytic enzymes
Elimination half-life20 (16–22) days
Identifiers
CAS Number
DrugBank
ChemSpider
  • None
UNII
KEGG
Chemical and physical data
Molar mass149 000
 ☒NcheckY (what is this?)  (verify)

Mepolizumab, sold under the brand name Nucala, is a humanized monoclonal antibody used for the treatment of severe eosinophilic asthma. It recognizes and blocks interleukin-5 (IL-5), a signalling protein of the immune system.

Medical uses

Mepolizumab is approved by the U.S. Food and Drug Administration (FDA) for the maintenance treatment of severe asthma in patients aged 6 years[1] or older and with an eosinophilic phenotype in combination with other medicines used to treat asthma.[2] In Europe it is approved as an add-on treatment for severe refractory eosinophilic asthma in adult patients.[3]

In studies, mepolizumab cut the necessity for hospitalisation due to asthma exacerbations in half, as compared to placebo.[4]

In December 2017, the FDA expanded mepolizumab's indication to treat adults with eosinophilic granulomatosis with polyangiitis (EGPA), which is a rare autoimmune condition that can cause vasculitis.[5]

Side effects

Common side effects in clinical trials included headache (19% of patients under mepolizumab treatment versus 18% under placebo), reactions at the site of injection (8% versus 3%), infections of the urinary tract (3% versus 2%) and the lower respiratory tract, eczema and muscle spasms (both 3% versus <1%).[6][7]

Overdose

Single doses of 15 times the usual therapeutic dose have been tolerated in studies without significant side effects.[6][7]

Interactions

No interaction studies have been conducted. As with other monoclonal antibodies, the interaction potential is considered to be low.[6]

Pharmacology

Mechanism of action

Mepolizumab binds to IL-5 and prevents it from binding to its receptor, more specifically the interleukin 5 receptor alpha subunit, on the surface of eosinophil white blood cells. While eosinophils play a role in inflammation associated with asthma, the exact mechanism of mepolizumab is unknown.[7]

Pharmacokinetics

After subcutaneous injection, mepolizumab has an estimated bioavailability of 80% and reaches highest blood plasma concentrations after four to eight days. Like other antibodies, it is degraded by proteolytic enzymes. Its biological half-life is 20 days on average, ranging from 16 to 22 days in different individuals.[6][7]

Chemistry

The substance is an IgG1 kappa monoclonal antibody, the two heavy chains consisting of 449 amino acids each, and the two light chains consisting of 220 amino acids each. The protein part has a molar mass of about 146 kDa, and the sugar part of 3 kDa.[8]

History

Phase III clinical trials in severe eosinophilic asthma were completed in 2014. The FDA approved it in November 2015.[2] The European Commission granted a marketing authorisation valid throughout the European Union on 2 December 2015.[3]

Research

Mepolizumab has been investigated or is under investigation for the treatment of atopic dermatitis, hypereosinophilic syndrome (HES), eosinophilic esophagitis (EoE),[9] nasal polyposis, eosinophilic granulomatosis with polyangiitis (EGPA), and chronic obstructive pulmonary disease (COPD).

References

  1. ^ "FDA approves severe eosinophilic asthma treatment for children ages 6-11". AAP News. 2020-01-30.
  2. ^ a b "FDA approves Nucala to treat severe asthma" (Press release). U.S. Food and Drug Administration (FDA). 4 November 2016.
  3. ^ a b "Nucala EPAR Summary for the public" (PDF). European Medicines Agency. December 2015.
  4. ^ Yancey SW, Ortega HG, Keene ON, Mayer B, Gunsoy NB, Brightling CE, et al. (April 2017). "Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma". The Journal of Allergy and Clinical Immunology. 139 (4): 1167–1175.e2. doi:10.1016/j.jaci.2016.08.008. PMID 27726946.
  5. ^ "FDA approves first drug for Eosinophilic Granulomatosis with Polyangiitis, a rare disease formerly known as the Churg-Strauss Syndrome". U.S. Food and Drug Administration (FDA) (Press release). Retrieved 2017-12-13.
  6. ^ a b c d "Nucala Summary of Product Characteristics" (PDF). European Medicines Agency. December 2015.
  7. ^ a b c d FDA Professional Drug Information for Nucala.
  8. ^ "Nucala European Public Assessment Report" (PDF). European Medicines Agency. 24 September 2015. p. 10.
  9. ^ "Intravenous Mepolizumab in Children with Eosinophilic Esophagitis". U.S. National Library of Medicine. 3 September 2018.

External links

  • "Mepolizumab". Drug Information Portal. U.S. National Library of Medicine.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Mepolizumab&oldid=968403481"