Azvudine Cuts COVID-19 Deaths, Outperforming Paxlovid

COVID-19 has caused a global health crisis with over 776 million cases and 7 million deaths as of 2024. Despite vaccines reducing severe cases, treatment options remain critical for mitigating hospitalizations and mortality, particularly against evolving variants. Two widely used antivirals—Paxlovid and Azvudine—are central to current treatment protocols. However, their comparative efficacy and safety have been unclear until now.

A recent multicenter study, published in Signal Transduction and Targeted Therapy, reveals that Azvudine not only reduces all-cause mortality but also presents fewer adverse effects compared to Paxlovid.

Azvudine Study Overview

Study Design

The research was conducted in Henan and Xinjiang provinces, China, and involved:

• 37,606 hospitalized COVID-19 patients from 10 hospitals in Henan.
• 3,270 patients from a hospital in Xinjiang for additional validation.

Patients received eitherAzvudine or Paxlovid alongside standard care. Propensity score matching (PSM) was applied to balance demographic and clinical characteristics between groups.

Key Findings

Efficacy Outcomes

• Mortality Reduction:
  • Azvudine significantly reduced all-cause mortality (Hazard Ratio [HR]: 0.82, p = 0.036).
  • 469 deaths were recorded: 288 in the Azvudine group vs. 181 in the Paxlovid group.
• Composite Disease Progression:
  • No significant difference between the two groups (HR: 1.15, p = 0.097).
• Delayed Treatment:
  • Patients starting treatment 5+ days after diagnosis saw greater benefits with Azvudine (HR: 0.56).
• Patients with Malignant Tumors:
  • Azvudine provided notable advantages for these patients (HR: 0.33).

Safety Outcomes

This drug demonstrated fewer adverse events (AEs), particularly mild to moderate (grades 1 and 2), compared to Paxlovid, making it a safer alternative for hospitalized patients.

Antitumor Potential of Azvudine

In addition to its antiviral properties, Azvudine exhibited promising antitumor effects, including:

• Suppressing hepatocellular carcinoma cell proliferation.
• Enhancing immune responses, which could benefit COVID-19 patients with liver cancer.

Implications for COVID-19 Management

The findings support the use of Azvudine as a first-line treatment for:

• Hospitalized COVID-19 patients, particularly those with delayed treatment initiation.
• Patients with comorbidities, such as malignancies.

Azvudine’s dual benefits—lower mortality risk and antitumor effects—position it as a versatile option in the fight against COVID-19 and associated complications.

Future Directions

• Broader Validation: Further trials are needed to confirm these findings across diverse populations.
• Biomarker Studies: Identifying subgroups that would benefit most from Azvudine treatment.
• Antitumor Applications: Exploring its potential in oncology beyond the antiviral use.

Takeaway

Azvudine outperforms Paxlovid in reducing COVID-19 mortality, with fewer side effects and added antitumor benefits. These findings highlight the drug’s potential as a safer and more effective treatment, particularly for vulnerable patient populations.

More Information: Wang, H., Cui, G., Cheng, M. et al. (2025) 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. doi: https://doi.org/10.1038/s41392-025-02126-w. https://www.nature.com/articles/s41392-025-02126-w