Mepolizumab

Compound Name:MepolizumabMolecular Target:IL-5Molecular Structure:Humanized IgG1? monoclonal antibodyLicensed Indication:severe eosinophilic asthma in patients aged 12 years or olderManufacturer and/or Distributor:GlaxoSmithKlineInitial FDA Approval2015SummaryMepolizumab (Nucala) is the first approved biologic therapy that targets interleukin-5 (IL-5), which plays an important role in regulating the function of eosinophils, an inflammatory cell known to be important in asthma. It is administered as a 100 mg fixed dose subcutaneous injection every four weeks. Mepolizumab was licensed in November 2015 as an add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. Nucala is not approved for the treatment of other eosinophilic conditions or relief of acute bronchospasm or status asthmaticus. The mepolizumab Phase II/III clinical development program involved nine studies and over 1,300 patients. Three key clinical trials – DREAM (MEA112997), MENSA (MEA115588) and SIRIUS (MEA115575) –established the efficacy and safety profile of Nucala. Patients who were shown to benefit from treatment with mepolizumab in the Phase III clinical trials were those with blood eosinophil levels of 150 cells/µL or greater just prior to treatment. Systemic allergic/hypersensitivity reactions were reported by 1% of subjects who received Nucala compared to 2% of subjects in the placebo group. Manifestations included rash, pruritus, headache, and myalgia. The most common adverse reactions (≥3% and more common than placebo) reported in the first 24 weeks of two clinical trials with Nucala (and placebo) were headache, injection site reaction, back pain, fatigue, influenza, urinary tract infection, upper abdominal pain, pruritis, eczema, and muscle spasm. Herpes zoster infections have occurred in patients receiving Nucala.References

Package Insert: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Nucala/pdf/NUCALA- PI-PIL.PDF  

1. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1189-97.
 http://www.ncbi.nlm.nih.gov/pubmed/25199060

2. Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1198-207. http://www.ncbi.nlm.nih.gov/pubmed/25199059

3. Fainardi V, Pisi G, Chetta A. Mepolizumab in the treatment of severe eosinophilic asthma. Immunotherapy. 2016 Jan;8(1):27-34. 
http://www.ncbi.nlm.nih.gov/pubmed/26653083

4. Anderson WC 3rd, Szefler SJ. New and future strategies to improve asthma control in children. J Allergy Clin Immunol. 2015 Oct;136(4):848-59.
 http://www.ncbi.nlm.nih.gov/pubmed/26318072

5. Ann Allergy Asthma Immunol. 2016 Dec 3. pii: S1081-1206(16)31267-4. doi: 10.1016/j.anai.2016.10.028. [Epub ahead of print] Assessing the value of mepolizumab for severe eosinophilic asthma: a cost-effectiveness analysis. Whittington MD1, McQueen RB1, Ollendorf DA2, Tice JA3, Chapman RH2, Pearson SD2, Campbell JD4.

6. Clin Exp Allergy. 2017 Jan;47(1):129-138. doi: 10.1111/cea.12853. Epub 2016 Dec 8. Comparison of anti-interleukin-5 therapies in patients with severe asthma: global and indirect meta-analyses of randomized placebo-controlled trials. Cabon Y1, Molinari N1,2, Marin G1, Vachier I3, Gamez AS3, Chanez P4, Bourdin A2,3.

7. J Allergy Clin Immunol. 2016 Oct 4. pii: S0091-6749(16)30891-0. doi: 10.1016/j.jaci.2016.08.008. [Epub ahead of print] Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma. Yancey SW1, Ortega HG2, Keene ON3, Mayer B3, Gunsoy NB3, Brightling CE4, Bleecker ER5, Haldar P4, Pavord ID6.

8. Clin Ther. 2016 Sep;38(9):2058-2070.e1. doi: 10.1016/j.clinthera.2016.07.010. Epub 2016 Aug 21. Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study. Lugogo N1, Domingo C2, Chanez P3, Leigh R4, Gilson MJ5, Price RG6, Yancey SW7, Ortega HG8.

9. Lancet Respir Med. 2016 Jul;4(7):549-56. doi: 10.1016/S2213-2600(16)30031-5. Epub 2016 May 10. Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies. Ortega HG1, Yancey SW2, Mayer B3, Gunsoy NB3, Keene ON3, Bleecker ER4, Brightling CE5, Pavord ID6.

10. Allergy. 2016 Sep;71(9):1335-44. doi: 10.1111/all.12914. Epub 2016 May 24. Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment. Magnan A1, Bourdin A2, Prazma CM3, Albers FC3, Price RG4, Yancey SW3, Ortega H3.

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