International authoritative journal published: Ultra-large-scale comparison proves that the clinical efficacy of Azvudine is better than that of drug P

Recently, the top journal "Signal Transduction and Targeted Therapy" (with an impact factor of 40.8) under Nature, a scientific journal with a long history (founded in 1869) and great influence, published the largest multicenter retrospective study of azvudine versus nirmatrelvir‒ritonavir (Paxlovid) to date, "Real-world effectiveness and safety of oral azvudine versus nirmatrelvir‒ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort study" [1].

The study collected data from 40,876 hospitalized patients with COVID-19 infection in 11 hospitals in Henan and Xinjiang Uygur Autonomous Region from December 5, 2022 to January 31, 2023. After propensity score matching, 2,404 patients receiving azithromycin and 1,202 patients receiving Paxlovid were finally included. [2] Professor Yu Zujiang, Chief Physician Ren Zhigang and Academician Chang Junbiao of the First Affiliated Hospital of Zhengzhou University are the corresponding authors, and doctoral student Wang Haiyu, deputy chief physician Cui Guangying, senior engineer Cheng Ming, Professor Turgan Aili Aji of the First Affiliated Hospital of Zhengzhou University, and Chief Physician Li Guotao of Luoyang Central Hospital are the co-first authors. [3] They compared the clinical outcomes between the two drugs using Kaplan-Meier analysis and Cox regression models. In addition, in vitro and in vivo experiments were used to evaluate the anti-tumor effects and safety of the two drugs. [4] The main research results are as follows:

Azvudine reduced the risk of all-cause death by 18% compared with Paxlovid

Cox regression analysis showed that the risk of all-cause mortality in the azithromycin group was 18% lower than that in the Paxlovid group (HR = 0.82, 95% CI: 0.676–0.987, P = 0.036). Kaplan-Meier analysis showed that the cumulative mortality rate in the azithromycin group was significantly lower than that in the Paxlovid group (P = 0.038). [2]

Good safety, with lower adverse event rate than Paxlovid

The results of the study showed that the incidence of adverse events in the azvudine group was lower than that in the Paxlovid group, especially in terms of abnormal liver function and hematological indicators. [1][2]

Azvudine significantly inhibits cancer cells and improves patients' immunity

In the subgroup analysis, it was unexpectedly found that azithromycin tablets had a more significant advantage in patients with malignant tumors, reducing the risk of all-cause mortality by 67% (HR = 0.33, P < 0.001) and the risk of composite disease progression by 46%. [2] In vitro and in vivo experiments also demonstrated the significant anti-tumor activity of azithromycin:

- In vitro experiments showed that azithromycin significantly inhibited the proliferation and invasion of hepatocellular carcinoma (HCC) cells, while Paxlovid had no such effect. [1]

- In vivo experiments showed that azithromycin could significantly inhibit the growth of HCC xenografts. [4]

- Single-cell RNA sequencing analysis showed that azithromycin can significantly change the tumor immune microenvironment, increase the proportion of CD4+T cells and CD8+T cells, and regulate signal transduction between immune cells. [1]

These groundbreaking research results not only lay a solid experimental foundation for the potential application of azithromycin in the field of tumor treatment. It also provides strong evidence for its expansion into the development of various tumor indications such as liver cancer, lung cancer, and colorectal cancer. In September 2024, the clinical trial application (IND) for azithromycin for the treatment of solid tumors was approved by the National Medical Products Administration, and Phase I clinical trials were launched in Shanghai in January 2025. The IND application for the combination therapy of azithromycin/doxitinib for the treatment of non-small cell lung cancer was submitted to the CDE for review in November 2024. If successfully developed, it will provide newer and better treatment options for the clinical treatment of tumors and create huge social and economic value.

In summary, azithromycin can not only significantly inhibit the proliferation and invasion of cancer cells, but also effectively enhance the patient's immunity, especially in patients with COVID-19 infection who suffer from malignant tumors (especially hepatocellular carcinoma), showing more significant clinical benefits. [1][2] In addition, compared with Paxlovid, azithromycin has shown better efficacy and safety in reducing the all-cause mortality of hospitalized COVID-19 patients . As a representative of 3CL protease inhibitors, Paxlovid's real-world clinical research data based on a large sample size further confirms the excellent performance of azithromycin in the treatment of COVID-19, providing a valuable reference for clinicians and patients when choosing COVID-19 treatment drugs.

References:

1. Wang, H., Cui, G., Cheng, M. et al. Real‐world effectiveness and safety of oral azvudine versus nirmatrelvir‒ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort study. Sig Transduct Target Ther 10, 30 (2025).

2. [Dahe Daily] After two years, this medical team in Henan used solid data to "vindicate" the first domestically produced oral COVID-19 drug

3. [The First Affiliated Hospital of Zhengzhou University] Contributing "Chinese wisdom" to the world! Two research results of Yu Zujiang's team were published in internationally renowned journals

4.【iNature】STTT丨Zhengzhou University Ren Zhigang/Yu Zujiang/Chang Junbiao collaborative study found that avudine may provide greater clinical benefits for HCC patients