The "COVID-19 Oral Drug" is here! Virus, retreat! Retreat! Retreat!

On July 25, the National Medical Products Administration announced that it would conduct an emergency review and approval in accordance with the special drug approval process, and conditionally approved the registration application of Henan Zhenzhen Biotechnology's Azvudine Tablets to add the indication of treating COVID-19 . This also marks that China has ushered in a new oral small molecule drug for COVID-19 that has been independently developed.

Azvudine is an inhibitor of nucleoside reverse transcriptase and accessory protein Vif . In July last year, the National Medical Products Administration conditionally approved the marketing of Azvudine tablets for use in combination with nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors to treat adult HIV-1 (HIV) infected patients with high viral loads.

How can drugs used to treat HIV-1 infection be used to treat COVID-19?

This involves a concept called " new uses for old drugs ", which refers to drugs originally used to treat a certain disease, but can be used to treat another new disease because of the common mechanism. If we make an analogy, azithromycin and its viral target are like the relationship between a key and a lock. After the key is inserted into the lock, it can block the keyhole and destroy its function.

Different viruses sometimes have targets with similar active structures (similar to locks with similar keyhole structures), so in early papers, researchers pointed out that azithromycin may also be used to inhibit hepatitis B and hepatitis C viruses. Recently, there is evidence that it can inhibit the viral RNA-dependent RNA polymerase (RdRp) of the new coronavirus, which is the mechanism by which it can inhibit the new coronavirus .

In the previous application for listing submitted to the National Medical Products Administration, Real Biotech attached the results of the Phase III registration clinical trial. The press release pointed out that Azvudine can significantly improve clinical symptoms, that is, "it can significantly shorten the time for symptom improvement in patients with moderate COVID-19 infection pneumonia, increase the proportion of patients with improved clinical symptoms, and achieve clinically superior results."

In addition, Azvudine also "has the activity of inhibiting the new coronavirus, and the virus clearance time is about 5 days ." In terms of safety, "Azvudine tablets are generally well tolerated" and "do not increase the risk to the subjects."

This approval is a conditional approval of a new indication for the treatment of adult patients with common COVID-19. According to the relevant work procedures of the State Food and Drug Administration, "conditional approval for marketing" is to encourage "clinical value-oriented drug innovation and accelerate the marketing of clinically urgently needed drugs with outstanding clinical value" . Eligible drugs include drugs urgently needed in public health and vaccines urgently needed for major public health emergencies. This practice is not uncommon during the COVID-19 period. Pfizer's COVID-19 treatment drug Paxlovid was also approved through the same route.

After a drug is conditionally approved for marketing, the National Medical Products Administration also requires the drug marketing authorization holder to take corresponding risk management measures and complete relevant research such as drug clinical trials within the prescribed period as required , and submit a supplementary application. If the post-marketing study proves that its benefits outweigh the risks and the review is passed, a drug registration certificate with a validity period of 5 years will be reissued, and the certificate validity period will be counted from the date of approval of the marketing application.

If the research cannot prove that the benefits outweigh the risks, the Center for Drug Evaluation will make a disapproval review conclusion, and the National Drug Administration will cancel its drug registration certificate according to procedures. If the drug marketing authorization holder fails to complete the research and submit a supplementary application as required within the time limit, the National Drug Administration will cancel its drug registration certificate according to procedures.

Oral COVID-19 drugs are an important part of controlling the COVID-19 pandemic, and they have added new members to our arsenal after vaccines and antibody drugs. With the efforts of new drug developers, we hope that we can make the epidemic less scary soon.

Author: Ye Shi

Review | Tang Qin, Chief Researcher, Science Popularization Department, Chinese Medical Association

References:

[1] The National Medical Products Administration conditionally approved the marketing of Azvudine Tablets (https://www.nmpa.gov.cn/yaopin/ypjgdt/20210721142223181.html?type=pc&m=)

[2] Azvudine, A Novel Nucleoside Reverse Transcriptase Inhibitor Showed Good Drug Combination Features and Better Inhibition on Drug-Resistant Strains than Lamivudine In Vitro (doi: 10.1371/journal.pone.0105617)

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