Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 382

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 4
Chunk 382
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 is a potent and selective inhibitor of MET, an enzyme which functions abnormally in many types of solid tumors. We designed savolitinib to address human metabolite-related renal toxicity, the primary issue that halted development of several other selective MET inhibitors. In clinical studies to date, savolitinib has shown promising signs of clinical efficacy in patients with MET gene alterations in NSCLC, PRCC, CRC and GC with an acceptable safety profile. We partner with AstraZeneca to develop and commercialize savolitinib globally. For more information, see “—Overview of Our Collaborations—AstraZeneca.”
Savolitinib Mechanism of Action
MET is a signaling pathway that has specific roles in normal mammalian growth and development. However, the MET pathway has also been shown to function abnormally in a range of different cancers, primarily through MET gene amplification, protein overexpression and gene mutations. The aberrant activation of MET plays a major role in cancer pathogenesis, including tumor growth, survival, invasion, metastasis, the suppression of cell death as well as angiogenesis. MET also plays a role in drug resistance in many tumor types. MET gene aberrations has been found in NSCLC and CRC following EGFR TKI treatment, leading to drug resistance. MET dysregulation plays a role in the immunosuppression and pathogenesis of kidney cancer.
Savolitinib Regulatory Status and Path
In June 2021, the NMPA conditionally approved savolitinib for 2L NSCLC with METex14 skipping alterations, making savolitinib the first-in-class selective MET inhibitor in China. This approval follows a priority review designation by the NMPA in July 2020. The approval by the NMPA was based on positive results from a China Phase II trial in 2L NSCLC patients with METex14 skipping alteration, including patients with the more aggressive pulmonary sarcomatoid carcinoma subtype. 
In January 2025, supplemental NDA for savolitinib was approved by the NMPA for 1L NSCLC with METex14 skipping alteration. The NMPA also converted prior conditional approval in 2L patients to full approval. The new label included both treatment-naïve and previously treated patients in China. The approval was based on data from a confirmatory China Phase IIIb clinical trial (NCT04923945). Preliminary efficacy and safety data from the first-line cohort were presented at WCL