Breaking News: Genuine Biotech’s Azvudine Granted Phase IIa Clinical Trial Approval for Hematological Malignancies

Recently, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) has granted approval to Henan Genuine Biotech Co., Ltd. (Genuine Biotech) to initiate a Phase IIa clinical trial of its GEN-725 Tablets (Azvudine), intended for the treatment of hematological malignancies. This approval marks an important milestone in the clinical development of Azvudine for hematological malignancy treatment.

Azvudine is the first nucleoside oral anti-HIV drug approved in China for which Genuine Biotech holds proprietary rights. The product has amassed R&D and safety data across indications such as anti-HIV-1 and anti-COVID-19. This Phase IIa approval for hematologic malignancies further extends its potential for clinical application in oncology.

Hematologic malignancies—mainly including lymphomas, multiple myeloma, and various forms of leukemia—are among the most prevalent malignant tumors in China. They have long been associated with challenges such as limited treatment options, high recurrence rates, and poor prognosis. Particularly for subtypes like acute adult T-cell leukemia/lymphoma, in the absence of allogeneic transplantation, the median survival time of patients is less than 8 months, highlighting a pressing unmet clinical need.

Previous studies reveal that Azvudine, a nucleoside analog with a well-defined mechanism of action, works through two pathways to fight tumors: First, it is internalized by cells and integrated into DNA strands, thereby effectively inhibiting the DNA synthesis of tumor cells and directly inducing tumor cell death; second, it can exert additional anti-tumor effects by modulating the immune response.

This unique dual mechanism of action provides a solid scientific foundation for its clinical efficacy. A study published in Frontiers of Medicine in November 2025 further validated these findings: On the one hand, its anti-tumor activity as a nucleoside analog is closely correlated with the expression level of deoxycytidine kinase (dCK) in tumor cells; on the other hand, it boosts the infiltration and expansion of CD8+ T cells and NK cells by inhibiting the differentiation/aggregation of immunosuppressive cells, especially myeloid-derived suppressor cells (MDSCs), in the tumor microenvironment, and is correlated with the regulation of immune factors.

In in vitro CTG proliferation inhibition assays, Azvudine exhibited an IC50 of ≤ 0.1 μM on 11 lymphoma, 10 leukemia, and 2 myeloma cell lines; moreover, it demonstrated proliferation inhibitory activity that was comparable to or superior to that of cytarabine in multiple lymphoma, leukemia, and myeloma cell lines.

In vivo, Azvudine showed stable and dose-dependent anti-tumor activity in various hematological malignancy animal models. In the PDX model of human Burkitt lymphoma, Azvudine monotherapy achieved a tumor inhibition rate of 84.46%, and the combination therapy of Azvudine and cyclophosphamide (CTX) increased this rate to 100%. In the orthotopic syngeneic transplantation model of murine B-cell lymphoma A20-Luc, Azvudine monotherapy exhibited significant efficacy with a clear dose-dependent effect.

Azvudine’s oral dosage form is expected to offer a more accessible medication choice for some patient populations. Its robust safety and tolerability profiles, which have been established in prior clinical trials for other therapeutic indications, provide a valuable reference for its subsequent development in oncology. Notably, the above preclinical and cross-indication evidence still requires further systematic validation in prospective clinical studies involving patients with hematologic malignancies.

The newly approved Phase IIa clinical trial will build on prior research to further evaluate the safety and preliminary efficacy of Azvudine in patients with hematologic malignancies. As clinical research firmly advances, this project is anticipated to generate meaningful insights and viable solutions to address unmet clinical needs, bringing renewed hope to patients in need.