Lebrikizumab

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]

Lebrikizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetIL-13
Clinical data
Other namesMILR1444A, RG3637, TNX-650
Routes of
administration		Subcutaneous
ATC code
  • None
Identifiers
CAS Number
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6434H9972N1700O2034S50
Molar mass145287.42 g·mol−1
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As of 2021, 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

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
  1. "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.
  2. "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.
  3. Clinical trial number NCT00441818 for "Safety and Efficacy Study of TNX-650 to Treat Refractory Hodgkin's Lymphoma" at ClinicalTrials.gov
  4. 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
  5. 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.
  6. Almirall: Our late stage Pipeline Archived 14 May 2023 at the Wayback Machine
  7. "Prous Science Molecule of the Month: Lebrikizumab". Thomson Reuters. October 2011. Archived from the original on 26 October 2011. Retrieved 15 December 2011.
  8. 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)
  9. "Ebglyss: Pending EC decision". European Medicines Agency. 15 September 2023. Archived from the original on 20 September 2023. Retrieved 24 September 2023.
  10. "FDA Rejects Lilly's Eczema Treatment Over Third-Party Manufacturing Issues". BioSpace. Retrieved 3 October 2023.
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