Mepolizumab
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized (from mouse) |
| Target | IL-5 |
| Clinical data | |
| Trade names | Nucala |
| AHFS/Drugs.com | nucala |
| Routes of administration | Subcutaneous injection |
| ATC code | L04AC06 (WHO) |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Bioavailability | 80% (estimate) |
| Protein binding | None |
| Metabolism | Proteolytic enzymes |
| Biological half-life | 20 (16–22) days |
| Identifiers | |
| CAS Number |
196078-29-2  |
| PubChem (SID) | 47206675 |
| DrugBank |
DB06612 |
| ChemSpider | None |
| UNII |
90Z2UF0E52 |
| KEGG |
D04923  |
| Chemical and physical data | |
| Molar mass | ~149 kg/mol |
| (what is this?) (verify) | |
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
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]
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%).[4][5]
Overdose
Single doses of 15 times the usual therapeutic dose have been tolerated in studies without significant side effects.[4][5]
Interactions
No interaction studies have been conducted. As with other monoclonal antibodies, the interaction potential is considered to be low.[4]
Pharmacology
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.[4][5]
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.[6]
History
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
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
- 1 2 "FDA approves Nucala to treat severe asthma". FDA. 4 Nov 2016.
- 1 2 "Nucala EPAR Summary for the public" (PDF). European Medicines Agency. December 2015.
- ↑ 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.
- 1 2 3 4 "Nucala Summary of Product Characteristics" (PDF). European Medicines Agency. December 2015.
- 1 2 3 FDA Professional Drug Information for Nucala.
- ↑ "Nucala European Public Assessment Report" (PDF). European Medicines Agency. 24 September 2015. p. 10.