Mepolizumab

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Mepolizumab
Monoclonal antibody
Type Whole antibody
Source Humanized (from mouse)
Target IL-5
Clinical data
Trade names Nucala
AHFS/Drugs.com nucala
License data
Routes of
administration
Subcutaneous injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 80% (estimate)
Protein binding None
Metabolism Proteolytic enzymes
Elimination half-life 20 (16–22) days
Identifiers
CAS Number
PubChem SID
DrugBank
ChemSpider
  • None
UNII
KEGG
Chemical and physical data
Molar mass ~149 kg/mol
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Mepolizumab (trade 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[edit]

Mepolizumab is approved by the U.S. Food and Drug Administration (FDA) for the maintenance treatment of severe asthma in patients aged 12 years or older and with an eosinophilic phenotype in combination with other medicines used to treat asthma.[1] In Europe it is approved as an add-on treatment for severe refractory eosinophilic asthma in adult patients.[2]

In studies, mepolizumab cut the necessity for hospitalisation due to asthma exacerbations in half, as compared to placebo.[3]

In December of 2017 the 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.[4]

Side effects[edit]

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%).[5][6]

Overdose[edit]

Single doses of 15 times the usual therapeutic dose have been tolerated in studies without significant side effects.[5][6]

Interactions[edit]

No interaction studies have been conducted. As with other monoclonal antibodies, the interaction potential is considered to be low.[5]

Pharmacology[edit]

Mechanism of action[edit]

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.[6]

Pharmacokinetics[edit]

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.[5][6]

Chemistry[edit]

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.[7]

History[edit]

Phase III clinical trials in severe eosinophilic asthma were completed in 2014. The FDA approved it in November 2015.[1] The European Commission granted a marketing authorisation valid throughout the European Union on 2 December 2015.[2]

Research[edit]

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

References[edit]

  1. ^ a b "FDA approves Nucala to treat severe asthma". FDA. 4 Nov 2016. 
  2. ^ a b "Nucala EPAR Summary for the public" (PDF). European Medicines Agency. December 2015. 
  3. ^ Yancey, S. W.; Ortega, H. G.; Keene, O. N.; Mayer, B; Gunsoy, N. B.; Brightling, C. E.; Bleecker, E. R.; Haldar, P; Pavord, I. D. (2016). "Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma". The Journal of Allergy and Clinical Immunology. doi:10.1016/j.jaci.2016.08.008. PMID 27726946. 
  4. ^ Commissioner, Office of the. "Press Announcements - FDA approves first drug for Eosinophilic Granulomatosis with Polyangiitis, a rare disease formerly known as the Churg-Strauss Syndrome". www.fda.gov. Retrieved 2017-12-13. 
  5. ^ a b c d "Nucala Summary of Product Characteristics" (PDF). European Medicines Agency. December 2015. 
  6. ^ a b c d FDA Professional Drug Information for Nucala.
  7. ^ "Nucala European Public Assessment Report" (PDF). European Medicines Agency. 24 September 2015. p. 10.