Lebrikizumab
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized |
| Target | IL-13 |
| Clinical data | |
| Legal status | Investigational |
| Routes | Subcutaneous injection |
| Identifiers | |
| CAS number | 953400-68-5  |
| ATC code | None |
| UNII | U9JLP7V031  |
| KEGG | D09633 |
| Chemical data | |
| Formula | ? |
| (what is this?) (verify) | |
Lebrikizumab (INN) is a humanized monoclonal antibody and an experimental immunosuppresive drug for the treatment of asthma that cannot be adequately controlled with inhalable glucocorticoids. It has successfully completed a Phase II clinical trial.[1][2]
Mechanism of action
Lebrikizumab blocks interleukin 13 (IL-13), a cytokine (cell-signalling protein) that is produced by Th2 cells, a type of white blood cells. IL-13 is thought to induce the expression of another signalling protein, periostin, by epithelial cells of the bronchi. Periostin in turn seems to partake in a number of asthma related problems, such as bronchial hyperresponsiveness, inflammation, and activation and proliferation of airway fibroblasts, which are involved in airway remodelling.[2][3]
This theory is supported by the fact that patients with high periostin levels responded significantly better to lebrikizumab in the Phase II study: the forced expiratory volume in 1 second (FEV1) was 8.2% higher than under placebo in this group (measured from the respective baselines), while low-periostin patients had 1.6% higher FEV1, and the average value for all patients was 5.5%. The FEV1 increase in low-periostin patients was not statistically significant.[4]
Side effects
In the study, musculoskeletal side effects were more common under lebrikizumab than under placebo (13.2% versus 5.4%). Other side effects were comparable in both groups: infections overall 48.1% versus 49.1%, upper airway infections 12.3% versus 14.3%, and severe side effects overall 3.8% (treatment) versus 5.4% (placebo).[4]
References
- ↑ ClinicalTrials.gov NCT00930163 A Study of Lebrikizumab (MILR1444A) in Adult Patients With Asthma Who Are Inadequately Controlled on Inhaled Corticosteroids (MILLY)
- ↑ 2.0 2.1 Kraft, M. (2011). "Asthma Phenotypes and Interleukin-13 — Moving Closer to Personalized Medicine". New England Journal of Medicine 365 (12): 1141–1144. doi:10.1056/NEJMe1108666. PMID 21879891.
- ↑ "Prous Science Molecule of the Month: Lebrikizumab". Thomson Reuters. October 2011.
- ↑ 4.0 4.1 Corren, J.; Lemanske, R. F.; Hanania, N. A.; Korenblat, P. E.; Parsey, M. V.; Arron, J. R.; Harris, J. M.; Scheerens, H.; Wu, L. C.; Su, Z.; Mosesova, S.; Eisner, M. D.; Bohen, S. P.; Matthews, J. G. (2011). "Lebrikizumab Treatment in Adults with Asthma". New England Journal of Medicine 365 (12): 1088–1098. doi:10.1056/NEJMoa1106469. PMID 21812663.
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