Azacitidine

The pathogenesis of hematological malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is closely related to abnormal DNA methylation. The advent of demethylating drugs has provided a brand-new treatment path for patients who cannot tolerate intensive chemotherapy. Azacitidine is a typical representative of demethylating drugs of the cytosine nucleoside analog category. It binds to DNA methyltransferase to reduce the genomic methylation level and restore the normal expression of tumor suppressor genes. Meanwhile, it can be directly incorporated into cellular DNA and RNA to inhibit their synthesis, inducing the differentiation and apoptosis of tumor cells. At present, this drug is the first-line treatment option for patients with low-risk MDS and elderly patients/ patients intolerant to intensive chemotherapy for AML. It can also be used for the clinical treatment of chronic myelomonocytic leukemia, significantly prolonging the overall survival of such patients.

In recent years, the global market size of azacitidine has been stable at around USD 1.2 billion. The growth rate of the Chinese market is higher than the global average, with a compound annual growth rate of 18%, and the domestic market size exceeded RMB 1.8 billion in 2023. From the perspective of the competitive landscape, the original research product still accounts for nearly 35% of the market share. Domestic generic preparations continue to gain volume due to their cost-effectiveness advantages. At present, azacitidine preparations from 6 domestic enterprises have been approved for marketing, among which 3 varieties have been included in the national centralized volume-based procurement, with the highest price cut of the winning bids exceeding 85% compared with the original research product, which has greatly improved clinical accessibility.

The original research enterprise of azacitidine is Bristol-Myers Squibb, and the original research trade name is Vidaza®. Its US compound patent expired in 2013, and the core patent in China expired in 2019. The main dosage forms of the original research product include azacitidine for injection (specification: 100mg/vial) and oral azacitidine tablets (specification: 300mg/tablet). Both dosage forms have been included in the *Catalogue of Reference Preparations for Chemical Drugs* of China, and are also reference preparations recognized by the FDA. At present, there are more than 20 domestic registration numbers of azacitidine active pharmaceutical ingredients, among which 12 are in status A and can be used in association with preparation declaration. Both the original research and generic preparations of the two dosage forms have been approved for marketing in China. (Data as of October 2024, please refer to the official website of CDE for the latest information)

CATO can provide a full set of azacitidine impurity reference standards, covering starting materials, intermediates, by-products and degradation impurities involved in the synthetic route. All products meet the requirements of the Chinese Pharmacopoeia and relevant FDA regulations. Most impurities are available in stock for a long time. Orders placed before 16:00 can be shipped on the same day, which can fully meet the reference standard needs of enterprises in the whole process of API research and development, registration declaration and quality control.