"Jie" Gong "Times", "An" Heart Choice - Professor Zhang Fujie interprets the clinical research progress of Azvedine anti-COVID-19

Professor Wang Guiqiang

•Professor, Chief Physician, Doctoral Supervisor, Department of Infectious Diseases and Liver Disease Center, Peking University First Hospital

• Director of the Department of Infectious Diseases, Peking University First Hospital

• Concurrently serves as the director of the Liver Disease Center

• Chairman of the Infectious Diseases Branch of the Chinese Medical Association, Vice Dean of the College of General Education

• Vice President of the Infectious Disease Physicians Branch of the Chinese Medical Doctor Association and Standing Committee Member of the Internal Medicine Physicians Branch

• Member of the Expert Advisory Committee of the National Immunization Programme

• Member of the Infectious Disease Standards Committee of the Health Commission

• Chairman of the Working Committee on the Rational Application of Antimicrobials of the Chinese Hospital Association

• Director of Beijing Medical Association, Chairman-designate of Infectious Diseases Branch

• Standing Committee Member of Infection Immunization Branch of Chinese Society of Immunology

• Director of China Medical Tribune

•Vice Chairman of the Board of Directors of China Hepatitis Prevention and Control Foundation⻓

• Member of the Expert Committee of the China Hepatitis Prevention and Control Foundation

Professor Zhang Fujie

• Professor of Infection Center of Beijing Ditan Hospital affiliated to Capital Medical University, doctoral supervisor

• Director of the AIDS Clinical and Research Center of Capital Medical University

• Member of the Drug Resistance Committee of the World Health Organization (WHO).

• Head of the HIV/AIDS Clinical Expert Working Group of the Health and Family Planning Commission

• Vice Chairman of the National Health Standards Infectious Disease Standards Committee

• Engaged in the clinical, teaching and scientific research of infectious diseases for 37 years, he is the first doctor in China to carry out HIV antiretroviral treatment

• Presided over the national "Eleventh Five-Year Plan", "Twelfth Five-Year Plan" and "Thirteenth Five-Year Plan" AIDS major projects, the Ministry of Science and Technology key research and development projects and the National Institutes of Health research and research, published more than 200 guiding scientific papers in Lancet and other journals, it cites more than 5000, h-index34

➤ Virology: FNC can significantly inhibit viral replication in the early stage of COVID-19 infection, reduce viral load, and shorten the negative time

➤ Clinical symptom improvement: Compared with the control group, FNC significantly improved the clinical symptom improvement of patients infected with the new coronavirus, promoted disease recovery, and shortened the length

➤ Safety: FNC is safe and well tolerated against COVID-19

First of all, Professor Wang Guiqiang said that since the new crown epidemic, everyone has paid great attention to the research and development of

Next, Professor Zhang Fujie introduced the current situation of new crown prevention and control, and made an in-depth interpretation

Patients have been shown to develop symptoms

➤FNC is a broad-spectrum RNA virus inhibitor that inhibits the novel coronavirus RNA-dependent RNA polymerase (RdRp) and blocks the extension of RNA (Figure 1
).

➤FNC is a nucleoside analogue that is embedded in viral RNA during RNA synthesis, eventually terminating RNA strand synthesis and viral replication
.

➤ The thymus gland is important for maintaining normal immune function, FNC can reduce thymus viral load, activate CD4+ and CD8+ cells, regulate the release of inflammatory factors such as IL-1β, INF-γ, TNF-α and IL-6, thereby reducing inflammatory response and organ damage
.

Figure 1 Mechanism of action of FNC ⁵

Based on FNC's good antiviral mechanism, the research team was approved by the State Food and Drug Administration to carry out prospectively designed, randomized, double-blind, placebo-controlled, multi-center FNC anti-COVID-19 clinical trials in China, Russia, and Brazil with the highest clinical trial standards for new drugs, and the trial used digital quantitative PCR (DDPCR) for viral load detection
.

China Clinical Trial Results ⁶

The research team evaluated
the inhibitory effect of FNC on the virus.

The results showed that the higher the baseline viral load, the stronger
the inhibitory effect of FNC.

On day 5, the reduction in viral load was greater in the FNC group than in the control group (Figure 2), which fully demonstrated the effectiveness
of FNC in treating patients with COVID-19 pneumonia.

A pooled analysis of adverse reactions in both the experimental and control groups (Figure 3) showed that FNC was generally safe and well
tolerated.

Figure 2 Comparison of the baseline change in viral load in the FNC group compared to the control group

Figure 3 The incidence of adverse reactions in FNC compared with the control group

Results of clinical trials in ^Brazil7

The final clinical status of the subjects in the experimental group was significantly improved
compared with the subjects in the control group.

Moreover, FNC can significantly improve the clinical status of moderately severe patients, significantly shorten the nucleic acid negative time and hospital stay, and show good safety, which is also conducive to reducing the disease burden of patients and improving prognosis
more efficiently.

Russian clinical trial results ⁸

The trial found that FNC can significantly shorten the time for patients to improve their clinical status, especially on day 7, the proportion of clinical improvement in the FNC group (WHO score ≥2 points higher than the baseline improvement) was significantly higher than that in the control group, achieving clinical efficacy results
.

No participants in the trial withdrew or died
due to adverse events.

At the same time, FNC can improve the clinical status of patients faster, shorten the length of hospital stay, and return to normal life
as soon as possible.

On August 9, 2022, the General Office of the National Health Commission issued the Notice on the Inclusion of Azifrimate Tablets in the Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia, recommending that FNC be used to treat ordinary patients
with novel coronavirus pneumonia.

The Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Ninth Edition) makes the following medication recommendations for ^FNC9:

In addition, at present, Azfedine tablets (1mg specification, 35 tablets / box) are priced at 270 yuan / box, an average of 7.
71 yuan / 1mg, and the daily treatment cost is 38.
57 yuan / person, and the National Medical Insurance Bureau has included azifdine tablets into the scope of medical insurance payment, and insured patients can be reimbursed in accordance with regulations when using them, which greatly increases the affordability and accessibility of patients' drugs and reduces the burden
of medical insurance.

FNC is the first oral anti-covid-19 drug approved by NMPA with completely independent intellectual property rights, and early application can rapidly reduce the viral load, significantly improve the clinical symptoms of patients with novel coronavirus infection, promote disease recovery, and shorten the hospital stay of
patients.

In terms of prevention, there is currently no approved drug for post-exposure prevention or asymptomatic infection of new crown in China, and in the future, FNC will explore the evidence-based basis
for post-exposure prevention and the use of drugs in asymptomatic infected people.

At the end of the FNC symposium, Professor Wang Guiqiang said that everyone is concerned about the prevention and control of the new crown epidemic in the future, of which vaccines and drugs are some indispensable conditions
.

Widespread vaccination is an important factor
in reducing severe illness and mortality.

At the same time, China also needs its own small molecule drugs, at present, FNC has been listed and added to the new crown diagnosis and treatment plan, which has played an important role in reducing viral load, improving clinical symptoms and facilitating oral treatment for patients, providing an important weapon
for new crown treatment.

References:

1.
Sun Zeyu,Chai Jiatong,Xu Jiancheng.
Research progress of the new coronavirus variant "Omi kerong"[J/OL].
Acta Virology:1-11[2022-08-22].

2.
https://nextstrain.
org/ncov/gisaid/global/6m?p=grid.

3.
 Cevik M, Kuppalli K, Kindrachuk J, Peiris M.
Virology, transmission, and pathogenesis of SARS-CoV-2 BMJ 2020; 371 :m3862 doi:10.
1136/bmj.
m3862

4.
 NIH COVID-19 Treatment Guidelines.

5.
Yu B, Chang J.
Signal Transduct Target Ther.
2020; 5(1):236.

6.
FNC China Phase III data

7.
FNC Brazil Phase III data

8.
FNC Russia Phase III data

9.
National Health Commission of the People's Republic of China.
Chinese Journal of Clinical Infectious Diseases,2022,15(2):81-89.