Takeda has received approval from the Japanese Ministry of Health, Labour and Welfare (MHLW) for Fruzaqla (fruquintinib) for the treatment of advanced or recurrent colorectal cancer (CRC) that has progressed after chemotherapy. This approval marks a significant advancement in the treatment landscape for CRC in Japan, where it is the most prevalent type of cancer.
Clinical Basis for Approval
The approval is primarily based on the results of the Phase III FRESCO-2 trial, a global study conducted in the US, Europe, Japan, and Australia. The trial evaluated fruquintinib plus best supportive care (BSC) versus placebo plus BSC in patients with previously treated metastatic CRC.
The FRESCO-2 trial met all primary and key secondary endpoints, demonstrating a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS). Specifically, the data showed consistent benefits among patients treated with fruquintinib, regardless of prior therapies received.
According to Dr. Takayuki Yoshino, Deputy Director of Hospital at the National Cancer Center Hospital East, the approval of fruquintinib offers new hope for patients with metastatic CRC, who have long needed additional effective treatment options. He emphasized the clinical significance of the FRESCO-2 study in demonstrating the impact of this treatment.
FRESCO-2 Trial Details
The FRESCO-2 trial (NCT04322539) was a multi-regional clinical trial involving patients with previously treated metastatic CRC. Key findings from the trial include:
- Overall Survival (OS): Fruquintinib demonstrated a statistically significant improvement in OS compared to placebo.
- Progression-Free Survival (PFS): Fruquintinib also showed a significant improvement in PFS.
- Safety Profile: The safety profile of fruquintinib in FRESCO-2 was consistent with previously reported fruquintinib monotherapy studies. Adverse reactions leading to treatment discontinuation occurred in 20% of patients treated with fruquintinib plus BSC versus 21% of those treated with placebo plus BSC.
The results of the FRESCO-2 trial were published in The Lancet in June 2023.
Colorectal Cancer in Japan
CRC is the most prevalent cancer in Japan, with an estimated 161,000 new cases and 54,000 deaths in 2023, according to the National Cancer Center’s statistics. While early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options.
Fruquintinib: A Novel Targeted Therapy
Fruquintinib is a selective oral inhibitor of all three VEGF receptors (VEGFR-1, -2 and -3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy.
Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau. Fruquintinib is marketed under the brand name FRUZAQLA.
Global Approvals
FRUZAQLA has been approved in the US in November 2023, in the EU in June 2024, in Switzerland in August 2024 and in Canada, Japan and the United Kingdom in September 2024. These approvals underscore the potential of fruquintinib as a valuable treatment option for patients with previously treated metastatic CRC worldwide.
