Trifluridine

Colorectal cancer is a highly prevalent gastrointestinal malignant tumor worldwide. For advanced patients with resistance to fluorouracil-based drugs, there has been a long-term clinical lack of high-efficiency post-line treatment options. Trifluridine is a nucleoside antimetabolite antitumor drug. Its mechanism of action is different from that of traditional fluorouracil-based drugs. It can be phosphorylated by thymidine phosphorylase and then embedded into the DNA of tumor cells, interfering with DNA synthesis and inhibiting cell proliferation. At the same time, it is combined with tipiracil, a thymidine phosphorylase inhibitor, to form a compound preparation, which can effectively improve the stability of the plasma concentration of trifluridine. At present, it is mainly used for patients with metastatic colorectal cancer who have failed previous standard treatments such as fluorouracil, oxaliplatin, and irinotecan, and can also be used for the post-line treatment of metastatic gastric cancer, providing a brand-new survival benefit path for drug-resistant patients.

The global market size of trifluridine compound preparations had exceeded 1.1 billion US dollars in 2023, with a compound annual growth rate maintained at around 8%. The growth momentum mainly comes from the continuous increase in the penetration rate of post-line treatment for gastrointestinal tumors. In terms of the domestic market, since trifluridine and tipiracil tablets entered domestic clinical practice in 2019, the terminal sales in public medical institutions had exceeded 700 million yuan in 2023. At present, the original research product still accounts for more than 70% of the market share. Generic drugs from 3 domestic enterprises have been approved for marketing and included in the centralized procurement. The price drop after centralized procurement has exceeded 80%, which further promotes the improvement of clinical accessibility, and the demand for localization of upstream API has also expanded rapidly accordingly.

The original research enterprise of trifluridine compound preparation is Japan's Taiho Pharmaceutical Co., Ltd., and the original research trade name is Lonsurf. The expiration time of its core compound patent in major markets such as Japan and the United States is 2020, and the expiration time of the compound patent in China is 2021. The main dosage form approved by the original research is tablets, with two specifications: each tablet contains 15mg of trifluridine / 7.065mg of tipiracil, and 20mg of trifluridine / 9.42mg of tipiracil. The original research dosage form has been included in the *Catalogue of Reference Preparations of Chemical Drugs* of China, and also listed in the FDA Reference Preparation Catalogue. At present, the trifluridine APIs of more than 10 domestic enterprises have completed registration in CDE and obtained Class A status, and the trifluridine and tipiracil tablets of another 6 enterprises have been approved for marketing. (Data as of November 2024, please refer to the official CDE website for the latest information)

CATO provides a full set of impurity reference standards for trifluridine, covering all kinds of known and potential impurities in the synthesis process and degradation pathways. All products meet the quality control requirements of multiple regulatory systems such as the Chinese Pharmacopoeia and FDA. Most products have sufficient spot stock. Spot orders placed before 16:00 can be shipped on the same day, which can fully meet the reference standard supply needs in the process of API R&D, quality research and consistency evaluation.