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On February 7, the website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced that the MEDI3506 injection (tozorakimab), submitted by AstraZeneca, is proposed to be included in the breakthrough therapy designation for the indication: aimed at providingHospitalized patients with viral pulmonary infections requiring oxygen therapyReduce the risk of progression to invasive mechanical ventilation (IMV)/extracorporeal membrane oxygenation (ECMO) and death.Public information shows that MEDI3506 is aPossibleMonoclonal Antibody Inhibiting IL-33 Function。
Screenshot source:CDE Official Website
According to literature reports,Interleukin-33 (IL-33)Is aFunctionThe extensive IL-1 family of cytokines is released from stressed or damaged barrier tissues, including endothelium and epithelium, following triggers by external factors such as trauma, allergen exposure, or infection. Under normal physiological conditions, IL-33 can initiate protective immune responses; however, excessive IL-33 release or chronic signaling may also drive tissue-damaging inflammation. Nearly two decades of preclinical evidence suggest that dysregulated IL-33 activity could be implicated in the pathology of inflammatory diseases like COVID-19 and severe infectious diseases.The therapeutic potential of anti-IL-33 antibodies has been preliminarily validated in studies targeting various diseases such as asthma, atopic dermatitis, and food allergies.。Tozorakimab is a novel therapeutic drug,With a dual mechanism of action. It can effectively inhibit IL-33-driven ST2 (IL-33 receptor)-dependent inflammatory responses and prevent the oxidation and activity of IL-33 through the RAGE/EGFR signaling pathway, thereby enhancing epithelial cell migration and repair. The upregulation of ST2 on other immune cells may be a significant driving factor for Type I inflammatory responses during respiratory viral exacerbations.
▲Introduction to MEDI3506 (Image Source: Reference [2])According to AstraZeneca's earlier disclosure, as a monoclonal antibody targeting IL-33,tozorakimabHas been demonstrated in Phase 1 clinical trials to be able toEffectively reduceChronic Obstructive Pulmonary Disease (COPD)Levels of Pro-Inflammatory Cytokines IL-5 and IL-13 in Patient Serum。According toClinicalTrialsAccording to the official website, tozorakimab is currently undergoing international multicenter Phase 3 clinical trials for multiple indications, including COPD, asthma, and hospitalized patients with viral pulmonary infections requiring oxygen therapy, among others. In China, this product is being developed for the treatment of patients with a history of acute exacerbations.COPDPatients hospitalized with viral pulmonary infections requiring oxygen therapy have also entered Phase 3 clinical trials.[1] Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Feb 7, 2024, from https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c[2] Respiratory & Immunology: emerging pipeline. Retrieved March 26, 2021, from https://www.astrazeneca.com/content/dam/az/Investor_Relations/events/Respiratory_and_Immunology_emerging_pipeline_presentation.pdf[3] England, E., Rees, D.G., Scott, I.C. et al.（2023） Tozorakimab (MEDI3506): an anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE/EGFR to reduce inflammation and epithelial dysfunction. Sci Rep. doi：https://doi.org/10.1038/s41598-023-36642-yThis article is from the content team of WuXi AppTec. Individuals are welcome to share it on their social media platforms, but unauthorized reproduction by media or organizations in any form to other platforms is prohibited. For authorization to reproduce, please contact us via a message on the "MedView" WeChat Official Account. For other collaboration inquiries, please contact wuxi_media@wuxiapptec.com.
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