HONG KONG, SHANGHAI, and FLORHAM PARK, N.J. – In a significant move for cancer treatment in China, HUTCHMED (China) Limited (Nasdaq/AIM:HCM; HKEX:13) and Innovent Biologics, Inc. (HKEX: 01801) have jointly announced that the China National Medical Products Administration (NMPA) has accepted for review their New Drug Application (NDA) for the combination of fruquintinib and sintilimab. The treatment targets patients with locally advanced or metastatic renal cell carcinoma who have previously failed treatment with a tyrosine kinase inhibitor (TKI).
This NDA is backed by compelling data from the FRUSICA-2 study, a randomized, open-label, active-controlled registration study. The study pitted the fruquintinib and sintilimab combo against axitinib or everolimus monotherapy in the second-line treatment of advanced renal cell carcinoma. Notably, the study met its primary endpoint: progression-free survival (PFS), as assessed by blinded independent central review (BICR) using RECIST 1.1 criteria. The combination therapy also showed promise in secondary endpoints, including objective response rate (ORR) and duration of response (DoR). The safety profile was deemed tolerable, with no new safety concerns emerging. The detailed findings from FRUSICA-2 are slated for presentation at an upcoming scientific conference.
“The challenges of kidney cancer in China are substantial, especially given the limited options available to patients after first-line therapies fail. This NDA for the fruquintinib and sintilimab combination in advanced renal cell carcinoma represents a critical step in addressing this unmet need,” stated Dr. Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED. “We are committed to delivering this combination therapy to patients battling renal cell carcinoma. Concurrently, our ongoing research is focused on unlocking the full potential of this treatment and expanding our pipeline across various cancers, ultimately aiming to provide patients with more effective treatment choices.”
Dr. Hui Zhou, Senior Vice President of Innovent, added, “The acceptance of the NDA for the sintilimab and fruquintinib combination signifies a substantial advance in delivering a more effective second-line treatment alternative for patients with advanced renal cell carcinoma in China. Our PD-1 inhibitor, sintilimab (TYVYT®), is solidifying its place as a core element of immuno-oncology (IO) therapy, and this marks its 10th indication, signifying a meaningful milestone in lifecycle management and clinical value optimization.”
This development follows a conditional NMPA approval in December 2024 for the same combination, fruquintinib and sintilimab, for treating patients with advanced mismatch repair proficient (pMMR) endometrial cancer. This approval was based on data from the FRUSICA-1 study.
**The Disease Landscape**
Globally, around 435,000 new cases of kidney cancer were diagnosed in 2022. In China alone, that number reached an estimated 74,000. Renal cell carcinoma makes up approximately 90% of these kidney tumor cases.
**The Science Behind the Therapy**
Fruquintinib is a highly selective oral inhibitor targeting VEGFR-1, -2, and -3. These receptors are key players in inhibiting tumor angiogenesis, or the growth of new blood vessels that feed tumors. The design of fruquintinib aims to minimize off-target kinase activity, thus achieving sustained target inhibition and enhancing its potential for combination therapy.
Fruquintinib is co-developed and co-commercialized in China by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE®. It’s approved for metastatic colorectal cancer in China, and has already been utilized to treat over 100,000 colorectal cancer patients since its market launch.
Outside of mainland China, Hong Kong and Macau, Takeda holds the exclusive worldwide license to develop, commercialize, and manufacture fruquintinib, marketing it under the brand name FRUZAQLA®. It has already been approved in the U.S., Europe, Japan, and numerous other countries for previously treated metastatic colorectal cancer.
**On the Horizon**
Single-agent targeted therapy is a primary option for initial treatment of advanced renal cell carcinoma in China. However, there’s an unmet need for those patients who have already undergone single-agent targeted therapy and have not responded. Early results from a Phase Ib/II trial of fruquintinib plus sintilimab highlighted promising efficacy and a favorable safety profile.
Sintilimab, known as TYVYT® (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody developed and commercialized by Innovent and Eli Lilly and Company. It is designed to bind to PD-1 molecules on T-cells, thus blocking the PD-1/PD-L1 pathway and reactivating T-cells to attack cancer cells.
Sintilimab has secured approval, and is included within the updated National Reimbursement Drug List (NRDL), for seven indications in China. Further, the eighth indication of sintilimab in combination with fruquintinib for advanced endometrial cancer was conditionally approved by the NMPA in December 2024.
**Looking Ahead**
Two NDAs for sintilimab are currently under NMPA review. These include use in combination with ipilimumab as a neoadjuvant treatment for resectable MSI-H/dMMR colon cancer, and in combination with fruquintinib for advanced renal cell carcinoma.
*Disclaimer: The statements contained in this article do not constitute medical advice.*
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