Recently, Tengsheng Bo Pharmaceutical Biotechnology Co., Ltd., the manufacturer of the first new coronavirus special drug in mainland China, ampavirus monoclonal antibody/romizumab injection, reached a strategic cooperation with Sinopharm Holdings Co., Ltd. to jointly promote the commercialization of the drug in China. The drug was developed by the Third People's Hospital of Shenzhen, Guangdong Province, Tsinghua University and Tengsheng Bo Pharmaceutical. How effective is it? Can you fight the Amikeron mutant strain? What is the difference with oral small molecule drugs? The reporter interviewed Lu Hongzhou, president of the Third People's Hospital of Shenzhen Municipality, Guangdong Province, head of the first shenzhen public health expert group on epidemic prevention and control, academician of the American Academy of Microbiology, and Zhang Zheng, director of the Shenzhen Institute of Liver Disease.
Reporter video connection screen. On the left is Lu Hongzhou, and on the right is Zhang Zheng.
Reporter: What are the technical characteristics of ambavir monoclonal antibody / romizumab injection? What are the team's new advances in COVID-19 vaccine and drug development so far?
Zhang Zheng: The neutralizing antibody drug we developed has 4 characteristics: First, it is very active in neutralizing the virus. Phase III trials conducted at 111 clinical trial sites in 6 countries on four continents showed that it reduced the risk of hospitalization and death in high-risk COVID-19 outpatients by 80%. Second, its broad spectrum is very good. At the beginning of 2020, we selected 206 potentially neutralizing antibodies from thousands of antibodies and screened out 2 antibodies that were highly effective in blocking COVID-19 infection as drug targets. At that time, the new crown virus variant was not yet prevalent, but practice proved that it could currently fight against mainstream variants, including Omilon. Third, this drug is a cocktail therapy formed by the combination of two antibodies, and these two antibodies are different sites that target the virus, which will reduce the possibility of drug mutations caused by the drug when applied, and can also better fight against future mutant viruses. Fourth, it is long-acting. We have made some modifications to the FC segment of the screened antibodies, prolonging the half-life of the antibodies, and after a clinical injection of a dose, the half-life of the antibodies can be as long as 3 to 6 months, while the half-life of ordinary antibodies is only about 3 weeks. Therefore, in the future, it can be applied to the prophylactic use of high-risk groups, vaccine non-responders or immunodeficient people.
Lu Hongzhou: Over the past two years, our team has done a lot of research on the question of how long the protective antibodies produced by the COVID-19 vaccine can last, and concluded that vaccination does avoid severe illness and death, but it cannot avoid being infected with the virus or not transmitting the virus to others.
Previous studies have concluded that vaccines that stimulate cellular immunity in humans are effective vaccines. In my opinion, nucleic acid vaccines are an important direction for future vaccine research and development. The principle of this vaccine is to enter the human body by injection or inhalation, which can simulate the process of virus replication in cells, stimulate cellular immunity, and protect the effect better and last longer. There is still a lack of inhalation vaccines in the domestic marketed vaccines, which is also our current research and development focus. The human respiratory tract is the first barrier of virus invasion, if you can develop an inhalation vaccine against the respiratory tract, so that the cells and mucous membranes of the respiratory tract produce protective antibodies, and have memory function, then when the human body encounters the virus, the respiratory tract as the first gate can prevent the infection and replication of the virus.
For mutated viruses, vaccination with one vaccine does not play a good preventive role, so it is also necessary to develop a universal vaccine, a polyvalent vaccine, or a universal vaccine. The ideal vaccination mode in the future is intramuscular injection and inhalation injection at the same time, which can play a good protective role, and everyone does not have to worry about being infected. Therefore, our scientific and technological strength should be more focused on the research of such vaccines, and in the future, we can even try to use nanotechnology for research and development.
Mainland China's first new coronavirus special drug amphavir monoclonal antibody / romizumab injection. (Courtesy of The Third People's Hospital of Shenzhen)
Reporter: The Aumecreon variant contains a large number of mutations, which are likely to escape from the previous antibodies and make the drug ineffective. Can ambavir monoclonal antibody/romizumab injection cope with the Omexjong variant? How do we deal with the ever-mutating coronavirus?
Zhang Zheng: At present, we and Tsinghua University, Tengsheng BoYao and other partners have carried out the neutralization activity of ampavirinumab/romizumab injection on the Omiljunn variant in laboratories at home and abroad, and the results show that the neutralization activity of the Omiljung variant is still maintained. It can maximize the limitation of the mutation of the virus in the human body, and it can also fight the immune escape caused by infection of the mutant strain. We now stock up on a broader, more efficient antibody portfolio of the second generation to be able to cope with a wide variety of variants that may emerge in the future. At the same time, it is being evaluated whether a new strategy of nasal intensive vaccination based on 2 to 3 doses of inactivated vaccine can prevent viral infection.
Lu Hongzhou: In the face of the constantly mutating new crown virus, drug research and development needs to be constantly changing. Viruses mainly rely on some key enzymes and key sites in the replication process, which are often relatively conservative and their characteristics are not easily changed. Finding these key enzymes and key sites for drug development can block the replication process of the virus, and our drugs will not fail because of the mutation of the virus. Therefore, there will be a breakthrough in basic research on the new crown virus, and there will be a breakthrough in vaccine and drug research and development.
Reporter: The "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Ninth Edition)" recommends two new crown drugs, amphavir monoclonal antibody/romimavir monoclonal injection and Pfizer's oral small molecule drug nematvir tablets/ritonavir tablets combination packaging (Paxlovid). How effective is Paxlovid? What are the therapeutic advantages of neutralizing antibody drugs such as ad-bavarumab/romizumab injection and oral small molecule drugs?
Lu Hongzhou: As a designated hospital for patients diagnosed with new coronary pneumonia in Shenzhen, we deployed the drug paxlovid from Pfizer for the first time in accordance with the idea of clinical research, and carried out prospective research on the use of this drug. Preliminary research results show that the daily amount of virus after taking the patient is decreasing, and the nucleic acid test turned negative on the 5th day of taking, that is, it was not contagious. After the virus in the patient's body disappears, the damage to various organs of the human body caused by the virus is also prevented. At present, this drug is mainly used in mild and ordinary patients at risk of severe illness, such as obesity, old age, patients with underlying diseases, and tumors, and it is not easy to develop into severe disease after use. We are also expanding the use of indications according to the situation, and strive for early use and multi-use, which can reduce the pressure of epidemic prevention and control as soon as possible.
At present, domestic small molecule drugs are also under research, and we are also working with the team of Professor Zhang Xumu of Southern University of Science and Technology to carry out related research. On the eve of the Spring Festival this year, our team conducted a virus suppression experiment on this small molecule drug being developed, and the results showed that the drug's inhibition effect on Omilon was more than 10 times stronger than that of similar foreign drugs, and we were also very optimistic about this drug, hoping to accelerate clinical trials and go public as soon as possible.
Zhang Zheng: Our neutralizing antibody therapy has a wider application window. Clinical trials have shown that the injection of this drug in the time window of the 0th to 5th day and 6th to 10th day after the onset of the disease has maintained a very good effect. Internationally approved small molecule drugs can only be applied in the first 5 days after the onset of illness in patients, and the time window for application is relatively short. However, small molecule drugs are oral drugs and are more convenient to use, while neutralizing antibody therapy must be given intravenously in a medical institution. However, these two drugs are not contradictory and can complement each other. Because from a clinical point of view, doctors need to treat patients according to the underlying disease, the condition of infection, etc., so there are also a variety of treatment options. We also hope that there will be more neutralizing antibody drugs and small molecule drugs that target different targets of the virus, and researchers can work together to maximize the containment of viral infections. (Reporter Zhang Chi, Hou Zhen)
More content, recommended for you
![Domestic new crown special drug is effective for Omicron! Zhong Nanshan: It is very valuable to promote in the world[fig]](data:image/gif;base64,R0lGODlhAQABAIAAAP///wAAACwAAAAAAQABAAACAkQBADs=)