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Lebrikizumab (INN) is a humanized monoclonal antibody and an experimental immunosuppressive drug for the treatment of asthma that cannot be adequately controlled with inhalable glucocorticoids. The drug was created by Tanox under the name TNX-650, and a phase I clinical trial for refractory Hodgkin’s lymphoma had been performed when Genentech acquired Tanox in 2007. It has successfully completed a Phase II clinical trial for the treatment of asthma.
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.
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.
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).
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- "anti-IL-13 humanized monoclonal antibody TNX-650". NCI Drug Dictionary. National Cancer Institute. Retrieved 10 December 2009.
- ClinicalTrials.gov NCT00441818 Safety and Efficacy Study of TNX-650 to Treat Refractory Hodgkin's Lymphoma
- ClinicalTrials.gov NCT00930163 A Study of Lebrikizumab (MILR1444A) in Adult Patients With Asthma Who Are Inadequately Controlled on Inhaled Corticosteroids (MILLY)
- 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.
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- 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.