Takeda Pharmaceutical Company has made a significant stride in the treatment of refractory metastatic colorectal cancer (mCRC) with the FDA approval of Fruzaqla (fruquintinib), a novel biomarker-agnostic therapy. This groundbreaking pill, which Takeda licensed from Hutchmed of China in a deal potentially worth $1.1 billion, represents the first major advancement in mCRC treatment for a broad patient population in over a decade.
Fruzaqla’s approval heralds a new era for mCRC therapy, offering a chemotherapy-free option that has demonstrated a survival benefit even after previous treatments have failed. This is particularly crucial for mCRC patients, who often suffer from the compounded effects of their disease and the exhaustion brought on by prior therapies. Teresa Bitetti, President of Takeda’s Global Oncology Business Unit, emphasized the critical need for new treatment avenues, acknowledging the limited options available until now.
The FDA’s endorsement of Fruzaqla is grounded in the results of two pivotal Phase 3 clinical trials, FRESCO and FRESCO-2. These studies revealed that Fruzaqla significantly extended overall survival (OS) and progression-free survival compared to placebo plus best supportive care. Specifically, median OS in the FRESCO-2 trial was 7.4 months for Fruzaqla recipients versus 4.8 months for the placebo group, and 9.3 months versus 6.6 months in the FRESCO trial.
Fruzaqla, which received fast-track designation from the FDA in 2020, is a selective oral inhibitor targeting VEGFR-1, -2, and -3, key factors in tumor angiogenesis, while minimizing off-target kinase activity. The drug is currently approved in China and awaits regulatory decisions in Europe and Japan.
The financial arrangement with Hutchmed includes an upfront payment of $400 million from Takeda for the rights to develop and commercialize Fruzaqla outside China, with up to $730 million in potential milestone payments and royalties on net sales.
Takeda’s journey in the gastrointestinal pipeline has seen mixed results, with the discontinuation of two other experimental drugs. The partnership with Theravance Biopharma was terminated following the failure of TAK-954 in a Phase 2b trial, and the development of sibofimloc, a Crohn’s disease treatment, was also halted.
However, Takeda has reasons to be optimistic, with two out of three anticipated U.S. approvals in the second half of the year already secured. Following Fruzaqla’s approval, Takeda also received FDA clearance for Adzynma (TAK-755) for congenital thrombotic thrombocytopenic purpura (cTTP), and anticipates approval for TAK-721 for eosinophilic esophagitis (EoE) by year’s end.
The urgency for new mCRC treatments is underscored by the statistics: approximately 153,000 new cases of CRC are expected to be diagnosed in the U.S. this year, with metastatic disease occurring in roughly 70% of patients, either at diagnosis or post-treatment. Globally, CRC ranks as the third most common cancer, resulting in 935,000 deaths in 2020 alone, as reported by the International Agency for Research on Cancer.
