CStone Pharmaceuticals announced the acceptance of the manufacturing localization application for the RET inhibitor GAVRETO® (pralsetinib) by the Center for Drug Evaluation of China National Medical Products Administration (NMPA). It is also worth noting that the manufacturing localization application for the precision therapy AYVAKIT® (avapritinib) was accepted in June 2023 and is currently under review, with CStone anticipating domestic supply in 2024. Recently, the government has implemented a range of supportive measures to encourage domestic drug manufacturing, including simplifying application procedures, providing clarity on regulatory pathways, and reducing the complexity of documentation requirements.

The NMPA's recent draft regulation suggests that applications for localized manufacturing may receive priority review. As a pioneer in this field, the company anticipates that these regulatory changes will expedite the approval and launch of domestically manufactured drugs allowing CStone to quickly expand into additional indication for GAVRETO and AYVAKIT. The manufacturing localization application of GAVRETO is the result of collaborative efforts between CStone, the foreign Marketing Authorization Holder (MAH), commercial partners, and domestic contract manufacturing organizations.

These efforts facilitated expedited technical transfer, including process optimizations, and commercial scale validation for both active pharmaceutical ingredient (API) and formulations of pralsetinib. Consistent manufacturing processes and quality standards have been applied to the domestically manufactured products as compared to the imported products, with human bioequivalence has been confirmed through a clinical study. From a company system perspective, CStone, as the MAH, has established commercial manufacturing capability by implementing a quality management system compliant with the latest national laws and regulations, meeting the requirements for MAH contract manufacturing and Good Manufacturing Practice (GMP).

GAVRETO was the first targeted RET inhibitor approved by the China NMPA and was initially approved in March 2021 for the treatment of locally advanced or metastatic RET fusion-positive non-small cell lung cancer (NSCLC) after platinum-based chemotherapy. It was also granted approval by the China NMPA as the first selective RET inhibitor for the treatment of advanced RET-altered thyroid cancer in March 2022. In June 2023, the China NMPA approved the supplemental new drug application (sNDA) of GAVRETO for the first-line treatment of adults with locally advanced or metastatic RET fusion-positive NSCLC.

To date, GAVRETO has obtained full approvals for first- and second-line indications in RET fusion-positive NSCLC in both the United States and Mainland China, also covering RET-altered thyroid cancer. Data from the global phase 1/2 ARROW study showed that GAVRETO exhibited potent and durable anti- tumor activity in patients with advanced RET fusion-positive NSCLC, RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer. Overall safety was generally manageable, with no new safety signals detected.

Additionally, GAVRETO demonstrated broad and persistent antitumor activity with manageable safety profiles in patients with various RET fusion-positive solid tumors, including pancreatic cancer and cholangiocarcinoma. These results have been published in top-tier international medical journals such as Lancet Oncology, Lancet Diabetes & Endocrinology, Nature Medicine, Annals of Oncology, and Thyroid. In addition, the efficacy and safety results of GAVRETO in Chinese patients with RET-mutant MTC were published in the highly cited endocrine and oncology journal Endocrine-Related Cancer in February 2024.

Following the prior publication of GAVRETO data in RET fusion-positive NSCLC in Chinese patients in June 2023 in Cancer, this publication marks another recognition from the international academic society, highlighting the significant academic and clinical value of GAVRETO. GAVRETO and AYVAKIT were discovered by CStone's partner, Blueprint Medicines. CStone has an exclusive collaboration and license agreement with Blueprint Medicines for the development and commercialization of GAVRETO and AYVAKIT in Greater China, which encompasses Mainland China Hong Kong, Macau and Taiwan.

In November 2023, CStone announced an exclusive agreement with Shanghai Allist Pharmaceuticals Co. Ltd.to commercialize GAVRETO in Mainland China.