Lebrikizumab
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized |
| Target | IL-13 |
| Clinical data | |
| Other names | MILR1444A, RG3637, TNX-650 |
| Routes of administration | Subcutaneous |
| ATC code |
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| Identifiers | |
| CAS Number | |
| ChemSpider |
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| UNII | |
| KEGG | |
| Chemical and physical data | |
| Formula | C6434H9972N1700O2034S50 |
| Molar mass | 145287.42 g·mol−1 |
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Lebrikizumab is a humanized monoclonal antibody and an investigational immunosuppressive medication for the treatment of asthma that cannot be adequately controlled with inhalable glucocorticoids. It 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.[1][2][3] It has successfully completed a Phase II clinical trial for the treatment of asthma.[4][5]
As of 2021[update], it is under a phase III clinical trial for the treatment of atopic dermatitis by Almirall with expected submission for approval in 2023 in the United States and the European Union.[6]
Mechanism of action
Lebrikizumab blocks interleukin 13 (IL-13), a cytokine (cell-signalling protein) that is produced by a type of white blood cell called Th2 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.[5][7]
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.[8]
Side effects
In the asthma 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 5.3% (placebo).[8]
Society and culture
Legal status
The European Medicines Agency Committee for Medicinal Products for Human Use recommended authorizing lebrikizumab (Ebglyss) for the treatment of atopic dermatitis.[9]
In September 2023, the FDA has declined to approve lebrikizumab due to certain findings during an inspection of a contract manufacturer, unrelated to the clinical trial data, safety or label for lebrikizumab.[10]
References
- ^ "First Patient Dosed In Phase 1 Trial Of Tanox, Inc.'s TNX-650 - News, Search Jobs, Events". Archived from the original on 3 March 2016. Retrieved 8 July 2008.
- ^ "anti-IL-13 humanized monoclonal antibody TNX-650". NCI Drug Dictionary. National Cancer Institute. Archived from the original on 25 September 2009. Retrieved 10 December 2009.
- ^ Clinical trial number NCT00441818 for "Safety and Efficacy Study of TNX-650 to Treat Refractory Hodgkin's Lymphoma" at ClinicalTrials.gov
- ^ Clinical trial number NCT00930163 for "A Study of Lebrikizumab (MILR1444A) in Adult Patients With Asthma Who Are Inadequately Controlled on Inhaled Corticosteroids (MILLY)" at ClinicalTrials.gov
- ^ a b Kraft M (September 2011). "Asthma phenotypes and interleukin-13--moving closer to personalized medicine". The New England Journal of Medicine. 365 (12): 1141–4. doi:10.1056/NEJMe1108666. PMC 4390041. PMID 21879891.
- ^ Almirall: Our late stage Pipeline Archived 14 May 2023 at the Wayback Machine
- ^ "Prous Science Molecule of the Month: Lebrikizumab". Thomson Reuters. October 2011. Archived from the original on 26 October 2011. Retrieved 15 December 2011.
- ^ a b Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, et al. (September 2011). "Lebrikizumab treatment in adults with asthma". The New England Journal of Medicine. 365 (12): 1088–98. doi:10.1056/NEJMoa1106469. PMID 21812663.
{{cite journal}}: CS1 maint: overridden setting (link) - ^ "Ebglyss: Pending EC decision". European Medicines Agency. 15 September 2023. Archived from the original on 20 September 2023. Retrieved 24 September 2023.
- ^ "FDA Rejects Lilly's Eczema Treatment Over Third-Party Manufacturing Issues". BioSpace. Retrieved 3 October 2023.
