HUTCHMED's ORPATHYS® and TAGRISSO® Combo Gains China's Breakthrough Therapy Status for Specific Lung Cancer

On December 11, 2024, HUTCHMED (China) Limited announced that their treatment combination of ORPATHYS® (savolitinib) and TAGRISSO® (osimertinib) has been granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation of China’s National Medical Products Administration (NMPA). This designation is specifically for patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) who have shown disease progression on EGFR inhibitor therapy and have MET amplification.

ORPATHYS® is a selective MET tyrosine kinase inhibitor, while TAGRISSO® is a third-generation, irreversible EGFR TKI. The treatment combination is under evaluation in China through the Phase III SACHI trial, which is a multi-center, open-label, randomized, controlled study. This trial compares the efficacy and safety of ORPATHYS® and TAGRISSO® with the standard platinum-based doublet chemotherapy in treating patients with MET-amplified, advanced NSCLC following failure of EGFR inhibitors. The primary endpoint of the study is progression-free survival, with secondary endpoints including overall survival, objective response rate, and safety.

The NMPA awards Breakthrough Therapy Designation to new drugs that show significant improvements over existing therapies for serious or life-threatening conditions without effective treatments. This status can expedite the drug's development and review process, potentially leading to conditional approval and priority review during the New Drug Application (NDA) submission. The significance lies in addressing the urgent needs of patients more swiftly.

Lung cancer is a leading cause of cancer-related deaths globally, with NSCLC accounting for 80-85% of cases. A substantial number of NSCLC patients are diagnosed at an advanced stage, with EGFR mutations present in a notable percentage of cases, particularly in Asia. MET is a crucial receptor in normal cell development, and its overexpression or amplification can lead to the proliferation of cancer cells and resistance to EGFR inhibitors. Among patients with NSCLC who progress after treatment with osimertinib, MET aberration is a common resistance mechanism, affecting 15-50% of these cases.

The combination of ORPATHYS® and TAGRISSO® has undergone extensive research in treating EGFR mutation-positive NSCLC. Notable studies include TATTON and SAVANNAH, which yielded promising results and led to several Phase III trials like SACHI, SANOVO, and the global SAFFRON trial. These trials focus on comparing the combination therapy to traditional chemotherapy options, aiming to offer a chemotherapy-free, biomarker-specific treatment that is orally administered and enhances the quality of life for lung cancer patients.

The SAVANNAH study recently completed recruitment, focusing on patients who progressed after osimertinib treatment due to MET amplification or overexpression. The US FDA recognized savolitinib and osimertinib’s combination as a Fast Track development program in 2023, emphasizing its potential impact on patient care.

ORPATHYS® received conditional approval in China for specific NSCLC cases, particularly those involving MET exon 14 skipping alterations. It is the first selective MET inhibitor approved in the country and has been part of the National Reimbursement Drug List since March 2023. Expanding its indication is under review, potentially covering treatment-naïve patients. With a significant portion of lung cancer patients located in China, this development holds substantial importance.

HUTCHMED and AstraZeneca have collaborated since 2011 to develop and commercialize ORPATHYS® globally. AstraZeneca manages its commercialization worldwide, while HUTCHMED handles its development and authorization within China. Meanwhile, TAGRISSO® continues to be a cornerstone in EGFR mutation-positive NSCLC treatment, with a robust evidence base from multiple Phase III trials, enhancing patient outcomes across various stages of the disease.

HUTCHMED is a biopharmaceutical company focusing on the discovery and commercialization of therapies for cancer and immunological diseases, with a significant workforce dedicated to oncology and immunology. The company has made substantial strides in bringing innovative cancer treatments from discovery to market, particularly in China and beyond.