The National Medical Products Administration (NMPA) website has indicated that Zai Lab Ltd’s (NASDAQ: ZLAB, HKG: 9688) Margenza (margetuximab), an Fc-engineered monoclonal antibody (mAb) targeting HER2 and developed by MacroGenics Inc., has been approved for the China market. The drug is indicated for the treatment of metastatic HER2-positive breast cancer patients who have received two or more anti-HER2 treatment schemes, with at least one for metastatic disease, combined with chemotherapy.
Margenza’s Mechanism of Action and Fc Optimization Technology
Margenza is an Fc-engineered monoclonal antibody that targets the HER2 oncoprotein. Similar to trastuzumab, Margenza inhibits tumor cell proliferation, reduces shedding of the HER2 extracellular domain, and mediates antibody-dependent cellular cytotoxicity (ADCC). The drug has been engineered to enhance the engagement of the immune system through MacroGenics’ Fc Optimization technology, resulting in greater in vitro ADCC and NK cell activation.
Partnership and Market Approval Process
Zai Lab struck a partnership with MacroGenics in November 2018, securing development and commercialization rights to Margenza and two other mAbs for the Greater China territory. The company filed the New Drug Application (NDA) based on results from the global Phase III SOPHIA study and a bridging study. Margenza, the only anti-HER2 treatment prolonging progression-free survival (PFS) in a head-to-head study with trastuzumab, was approved for marketing in the US in 2020 based on PFS data from the SOPHIA study. However, the SOPHIA study for the drug failed to reach the overall survival endpoint in September 2021. Its market filing was accepted for review by the NMPA in January this year.-Fineline Info & Tech
