Lebrikizumab

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Lebrikizumab ?
Monoclonal antibody
Type Whole antibody
Source Humanized
Target IL-13
Clinical data
Pregnancy cat.  ?
Legal status Investigational
Routes Subcutaneous injection
Identifiers
CAS number 953400-68-5 N
ATC code None
UNII U9JLP7V031 YesY
KEGG D09633 YesY
Chemical data
Formula  ?
 N(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]

[edit] 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]

[edit] 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]

[edit] References

  1. ^ ClinicalTrials.gov NCT00930163 A Study of Lebrikizumab (MILR1444A) in Adult Patients With Asthma Who Are Inadequately Controlled on Inhaled Corticosteroids (MILLY)
  2. ^ a b 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.  edit
  3. ^ "Prous Science Molecule of the Month: Lebrikizumab". Thomson Reuters. October 2011. http://www.prous.com/molecules/default.asp?ID=214. 
  4. ^ a b Corren, J.; Lemanske, R. F.; Hanania, N. A.; Korenblat, P. E.; Parsey, M. V.; Arron, J. R.; Harris, J. M.; Scheerens, H. et al. (2011). "Lebrikizumab Treatment in Adults with Asthma". New England Journal of Medicine 365 (12): 1088–1098. doi:10.1056/NEJMoa1106469. PMID 21812663.  edit
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