HUTCHMED (China) Limited has announced that its New Drug Application (NDA) for the combination of ORPATHYS® (savolitinib) and TAGRISSO® (osimertinib) has been accepted with priority review status by China's National Medical Products Administration (NMPA). This regulatory milestone targets patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) exhibiting MET amplification after disease progression on first-line EGFR inhibitor therapy.
The NDA is backed by data from the Phase III SACHI trial, a multi-center, open-label, randomized, controlled study. The trial evaluated the efficacy and safety of the ORPATHYS® and TAGRISSO® combination compared to standard platinum-based doublet-chemotherapy. Interim analysis showed the study met its primary endpoint of progression-free survival (PFS), leading to the conclusion of patient enrollment. The acceptance of the NDA also triggers a milestone payment from AstraZeneca to HUTCHMED.
Breakthrough Therapy Designation
In December 2024, the NMPA granted Breakthrough Therapy designation to the ORPATHYS® and TAGRISSO® combination. This designation is reserved for potential new treatments demonstrating substantial advantages over existing therapies for serious conditions, potentially accelerating the drug's development and review process.
Clinical Significance
Dr. Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED, stated, "This marks the first regulatory filing for the ORPATHYS® and TAGRISSO® combination... We hope to bring this all-oral, chemotherapy-free treatment option to patients with MET-driven lung cancer in the near future."
This combination addresses a critical unmet need in NSCLC treatment, particularly in patients who develop resistance to first-line EGFR inhibitors due to MET amplification. The all-oral regimen offers a chemotherapy-free alternative, potentially improving the quality of life for patients navigating this challenging disease.
NSCLC and MET Amplification
Lung cancer remains the leading cause of cancer death globally. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer cases. Among NSCLC patients, 10-15% in the US and Europe, and 30-40% in Asia, have EGFR-mutated NSCLC. MET amplification is a known mechanism of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) like osimertinib, occurring in approximately 15-50% of patients who progress after osimertinib treatment.
Ongoing Clinical Trials
The ORPATHYS® and TAGRISSO® combination has been extensively studied in EGFR mutation-positive NSCLC, including the TATTON and SAVANNAH trials. Encouraging results from these studies led to the initiation of three Phase III trials: SACHI and SANOVO (initiated in China) and the global SAFFRON study. These trials aim to establish the combination as a superior treatment option for patients with MET-amplified EGFR-mutated NSCLC.
About ORPATHYS® (savolitinib)
ORPATHYS® is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway. ORPATHYS® is already marketed in China and is under clinical development for multiple tumor types.
About TAGRISSO® (osimertinib)
TAGRISSO® is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. It has been used to treat nearly 800,000 patients across its indications worldwide.
