Shanghai, China, 14 January 2025 – AstraZeneca today announced that the National Medical Products Administration (NMPA) of China has officially approved ORPATHYS® (savolitinib tablets, hereinafter referred to as "savolitinib") for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition factor (MET) exon 14 skipping alterations. Concurrently, the NMPA has converted its prior conditional approval for savolitinib in pretreated patients to a full approval. The new indication for savolitinib in China will be expanded to cover both treatment-naive and pretreated patients.
Basis for Approval
The NMPA approval is based on data from a Phase IIIb confirmatory study (NCT04923945) conducted in patients with NSCLC harboring MET exon 14 skipping alterations. Preliminary efficacy and safety data from the first-line treatment cohort of the study were presented at the 2023 World Conference on Lung Cancer (WCLC) in September 2023, and the final study data were disclosed at the 2024 European Lung Cancer Congress (ELCC) in March 2024.
Savolitinib is China's first approved selective MET inhibitor, which AstraZeneca launched and commercialized under the trade name ORPATHYS® specifically for this patient population.
About NSCLC and MET Aberrations
Lung cancer is the leading cause of cancer-related deaths, accounting for approximately one-fifth of all cancer fatalities¹. China accounts for more than one-third of the global lung cancer patient population. Lung cancer is generally classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with NSCLC accounting for 80-85% of all lung cancer cases². The majority (around 75%) of NSCLC patients are diagnosed at an advanced stage. EGFR mutations are detected in approximately 10-25% of NSCLC patients in the United States and Europe, while the prevalence rate is as high as 30-40% among Asian patients.
MET is a receptor tyrosine kinase that plays a critical role in normal cellular development⁷. MET amplification or overexpression can drive tumor growth and cancer cell metastasis, and it is one of the major mechanisms underlying acquired resistance to EGFR tyrosine kinase inhibitor (TKI) therapy in patients with metastatic NSCLC harboring EGFR mutations. Approximately 2-3% of NSCLC patients have MET exon 14 skipping alterations, a targetable MET gene mutation. MET aberrations represent a key resistance mechanism to first/second-generation EGFR TKIs as well as third-generation EGFR TKIs such as osimertinib. Among patients who experience disease progression following osimertinib treatment, 15-50% develop MET aberrations¹⁰,¹¹,¹²,¹³,¹⁴. The incidence of MET aberrations may vary depending on sample type, detection method and assay thresholds employed.
About Savolitinib
Savolitinib is a potent, highly selective oral MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks the aberrant activation of the MET receptor tyrosine kinase signaling pathway caused by mutations (e.g., exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.
Savolitinib initially received conditional approval in China in June 2021 for the treatment of patients with NSCLC harboring MET exon 14 skipping alterations who had progressed after systemic therapy or were unable to tolerate chemotherapy. As China's first approved selective MET inhibitor, savolitinib has been included in the National Reimbursement Drug List since March 2023. Savolitinib is also being developed as a monotherapy or in combination with other agents for the treatment of various tumor types, including lung, renal and gastric cancers.
In 2011, Hutchison China MediTech (Chi-Med) and AstraZeneca entered into a global licensing agreement to jointly develop and commercialize savolitinib. The collaborative clinical development of savolitinib is led by Chi-Med in China and by AstraZeneca outside China. Furthermore, Chi-Med is responsible for the marketing authorization, manufacturing and supply of savolitinib in China, while AstraZeneca oversees the commercialization of savolitinib in China and globally. Sales revenue from savolitinib is recognized by AstraZeneca.
