Hutchmed secures priority review in China for ORPATHYS and TAGRISSO combination therapy

Hutchmed (China) Limited has achieved a significant milestone with the acceptance of its New Drug Application (NDA) by China’s National Medical Products Administration (NMPA) for the combination therapy of ORPATHYS (savolitinib) and TAGRISSO (osimertinib). This therapy targets patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations and MET amplification who have experienced disease progression after first-line EGFR inhibitor therapy. The granted priority review status highlights the treatment’s potential to address an urgent medical need.

This regulatory development not only underscores the innovation behind the therapy but also activates a milestone payment to Hutchmed from its global partner, AstraZeneca, as part of their ongoing collaboration.

What Does the ORPATHYS and TAGRISSO Combination Offer Lung Cancer Patients?

The combination of ORPATHYS and TAGRISSO represents a biomarker-driven treatment designed to overcome resistance mechanisms in NSCLC patients. MET amplification—a common driver of resistance to EGFR inhibitors—poses a significant challenge in managing lung cancer, often leaving patients with limited therapeutic options.

Unlike standard-of-care platinum-based chemotherapy, this combination is entirely oral, offering patients a more convenient and targeted therapy with the potential to improve both clinical outcomes and quality of life.

ORPATHYS, an oral and selective MET tyrosine kinase inhibitor (TKI), works by blocking aberrant activation of the MET receptor, which often contributes to tumor growth. TAGRISSO, a third-generation EGFR inhibitor, has already demonstrated efficacy in treating EGFR-mutant NSCLC, including cases with central nervous system metastases.

Key Clinical Trial Evidence Supporting the NDA

The NDA is supported by data from the SACHI Phase III trial, a pivotal study conducted in China. This trial compared the efficacy and safety of the ORPATHYS and TAGRISSO combination with platinum-based doublet chemotherapy, the current standard of care for patients with MET amplification.

Progression-free survival (PFS), the trial’s primary endpoint, was successfully met during an interim analysis conducted by an Independent Data Monitoring Committee (IDMC). Secondary endpoints such as overall survival (OS), objective response rate (ORR), and safety further bolstered the case for the therapy’s regulatory approval.

Beyond SACHI, the combination has been rigorously evaluated in global studies, including TATTON, SAVANNAH, and the ongoing Phase III trials SAFFRON and SANOVO. Each of these trials investigates the potential of ORPATHYS and TAGRISSO to address MET-driven resistance in EGFR-mutant lung cancer, paving the way for a more targeted approach to this challenging disease.

Breakthrough Therapy Designation and Global Collaboration

In December 2024, the NMPA granted Breakthrough Therapy designation for this combination, recognizing it as a potentially transformative treatment. The designation was based on substantial clinical evidence suggesting that the therapy offers significant advantages over existing options.

Hutchmed and AstraZeneca have collaborated on ORPATHYS since 2011, leveraging each company’s expertise to maximize the therapy’s reach and impact. While Hutchmed leads the development and regulatory processes in China, AstraZeneca manages commercialization globally.

ORPATHYS has already secured conditional approval in China for NSCLC patients with MET exon 14 skipping mutations. Its inclusion in China’s National Reimbursement Drug List (NRDL) in 2023 marked a critical step in making this innovative therapy widely accessible.

Expert Perspectives and Future Implications

Commenting on the development, Dr. Michael Shi, Chief Medical Officer of Hutchmed, emphasized the importance of a biomarker-specific approach in addressing resistance to EGFR inhibitors. He noted that the therapy’s chemotherapy-free, all-oral design has the potential to enhance both treatment continuity and patient quality of life.

The acceptance of the NDA with priority review could accelerate the availability of this therapy to patients in China, offering a new lifeline for those with MET-driven NSCLC. If approved, the therapy would solidify Hutchmed and AstraZeneca’s position as leaders in precision oncology, reshaping the treatment landscape for lung cancer.