Recently, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) approved Genuine Biotech Co., Ltd.'s GEN-725 tablets (Azvudine) for a Phase IIa clinical trial in the treatment of hematologic malignancies. This approval marks an important step forward in Azvudine's clinical development in the field of hematologic oncology.
Azvudine tablets are the first domestically approved nucleoside analog oral anti-HIV drug with independent intellectual property rights. The product has accumulated R&D and safety experience across indications including anti-HIV-1 and anti-COVID-19. This approval in hematologic malignancies further expands its clinical footprint in the oncology field.
Hematologic malignancies mainly include lymphomas, multiple myeloma, and various types of leukemia, representing one of the most prevalent types of malignant tumors in China. These conditions have long faced challenges such as limited treatment options, high relapse rates, and poor prognoses. Particularly for subtypes such as acute adult T-cell leukemia/lymphoma, in the absence of allogeneic transplantation, the median survival of patients is less than 8 months, representing a significant unmet clinical need.
Previous studies have shown that Azvudine, as a nucleoside analog with a well-defined mechanism of action, possesses a dual anti-tumor mechanism. On one hand, it is internalized by cells and incorporated into DNA strands, effectively inhibiting DNA synthesis in tumor cells and directly leading to tumor cell death. On the other hand, it exerts further anti-tumor effects through immunomodulation.
This unique dual mechanism serves as an important scientific basis supporting its clinical efficacy. A study published in Frontiers of Medicine in November 2025 further validated this: firstly, its anti-tumor activity as a nucleoside analog is closely related to the expression level of deoxycytidine kinase (dCK) in tumor cells; secondly, it can inhibit the differentiation/accumulation of immunosuppressive cells in the tumor microenvironment, particularly myeloid-derived suppressor cells (MDSCs), promote the infiltration and expansion of CD8+ T cells and NK cells, and is associated with the regulation of immune factors.
In in vitro CTG proliferation inhibition assays, Azvudine demonstrated IC50 values ≤ 0.1 μM across 11 lymphoma cell lines, 10 leukemia cell lines, and 2 myeloma cell lines. It also showed proliferation inhibitory activity comparable to or even superior to cytarabine across multiple lymphoma, leukemia, and myeloma cell lines.
In vivo, Azvudine demonstrated stable and dose-dependent anti-tumor activity in multiple hematologic malignancy animal models. In a human Burkitt lymphoma PDX model, Azvudine monotherapy achieved a tumor inhibition rate of 84.46%, and when combined with cyclophosphamide (CTX), the tumor inhibition rate reached 100%. In a mouse B-cell lymphoma A20-Luc orthotopic allograft model, Azvudine monotherapy showed significant efficacy with clear dose dependency.
Regarding the route of administration, Azvudine's oral formulation may offer a more convenient treatment option for some patients. On the safety front, Azvudine has accumulated extensive safety and tolerability experience from previous clinical studies in other indications, providing a reference basis for further exploration in the oncology field. It should be emphasized that the above preclinical and cross-indication evidence still requires further systematic validation in prospective clinical studies of patients with hematologic malignancies.
The Phase IIa clinical trial approved this time will build on previous research foundations to further evaluate the safety and preliminary efficacy of Azvudine in patients with hematologic malignancies. As subsequent clinical research progresses steadily, we look forward to this project providing effective solutions to unmet clinical needs and bringing new hope to patients in need.