Takeda Receives European Commission Approval for FRUZAQLA® (fruquintinib) for Metastatic Colorectal Cancer

HUTCHMED (00013) announced that its partner Takeda (TSE: 4502/NYSE: TAK) has received European Commission (EC) approval for FRUZAQLA.^®(Fruquintinib) as a monotherapy for the treatment of adult patients with metastatic colorectal cancer who have previously received standard treatments including fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy, anti-vascular endothelial growth factor (VEGF) therapy, anti-epidermal growth factor receptor (EGFR) therapy, as well as trifluridine-tipiracil or regorafenib treatment after disease progression or intolerance.

Following a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in April 2024, the European Commission granted this approval. The CHMP opinion was primarily based on the results of the FRESCO-2 international multicenter Phase III study, which also supported the submission of the Marketing Authorization Application (MAA). The MAA was validated and accepted by the European Medicines Agency (EMA) in June 2023. Data from the FRESCO-2 study were published in The Lancet in June 2023.

FRESCO-2 is an international, multicenter clinical trial conducted in the United States, Europe, Japan, and Australia, designed to investigate fruquintinib in combination with best supportive care versus placebo plus best supportive care for the treatment of patients with previously treated metastatic colorectal cancer (NCT04322539). FRESCO-2 met all primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful improvements in both overall survival (OS) and progression-free survival (PFS), with consistent benefits observed across patients receiving fruquintinib regardless of prior treatments. Fruquintinib exhibited a manageable safety profile in the FRESCO-2 study, consistent with previous reports from clinical trials on fruquintinib monotherapy. Among patients receiving fruquintinib plus best supportive care, 20% experienced adverse events leading to treatment discontinuation, compared to 21% in the placebo plus best supportive care group. The results of this study were presented at the European Society for Medical Oncology (ESMO) Congress in September 2022 and subsequently published in *The Lancet* in June 2023.

Fruquintinib is an orally administered inhibitor that selectively targets all three VEGFRs (VEGFR-1, -2, and -3). VEGFR inhibitors play a crucial role in suppressing tumor angiogenesis. Fruquintinib has been designed to possess higher kinase selectivity, aiming to reduce off-target kinase activity, thereby enabling greater drug exposure, sustained target coverage, and increased flexibility when potentially used as part of combination therapies. To date, fruquintinib has demonstrated a manageable safety profile, and studies on its combination with other anti-cancer therapies are ongoing.

Takeda holds the global exclusive license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong, and Macao. Fruquintinib was approved in the United States in November 2023 and is marketed by Takeda under the brand name FRUZAQLA.^®Market launch. The approval in the U.S. was based on data from two large, randomized, controlled Phase III clinical trials: the international multicenter clinical trial FRESCO-2 study and the FRESCO study conducted in China. Consistent benefits were demonstrated among a total of 734 patients treated with fruquintinib. The safety profiles of each study also remained consistent. In addition to the application submitted to the EMA, an application to Japan's Pharmaceuticals and Medical Devices Agency (PMDA) was also submitted in September 2023.

Fruquintinib has been approved for marketing in China and is commercialized under the brand name Elunate by HUTCHMED and Eli Lilly.^®(ELUNATE^®) for marketing. It was included in the National Reimbursement Drug List (NRDL) of China in January 2020. The Phase III pivotal registration study FRESCO, conducted in 416 Chinese patients with metastatic colorectal cancer, supported the approval of fruquintinib in China, and the results were published in the Journal of the American Medical Association (JAMA). As of mid-2023, more than 80,000 colorectal cancer patients in China have been treated with fruquintinib since its market launch in China.