Mepolizumab

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.

Mepolizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from mouse)
TargetIL-5
Clinical data
Trade namesNucala
AHFS/Drugs.comMonograph
MedlinePlusa615058
License data
Pregnancy
category
  • AU: B1
  • US: N (Not classified yet)
    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
     NY (what is this?)  (verify)

    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. "FDA approves Nucala to treat severe asthma" (Press release). U.S. Food and Drug Administration (FDA). 4 November 2016.
    3. "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. "Nucala Summary of Product Characteristics" (PDF). European Medicines Agency. December 2015.
    7. 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.
    • "Mepolizumab". Drug Information Portal. U.S. National Library of Medicine.
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