The first domestically-made new crown specific drug was approved for marketing, whether it can fight against mutant strains

China Business Daily (reporter Ma Jiawen/photo) On December 8, the first domestically produced anti-neovirus specific drug was approved by the State Food and Drug Administration for emergency listing. Compared with vaccines, new coronavirus antiviral drugs have attracted more attention.

New coronavirus neutralizing antibody combination therapy drugs needed by patients

Question: How effective is the new coronavirus specific antiviral drug _span4p1 span1p Where is the "special effect" of the medicine? On December 8, State Food and Drug Administration emergency approved Tengsheng Huachuang Medical Technology (Beijing) Co., Ltd. (hereinafter referred to as Tengsheng Huachuang) new coronavirus neutralizing antibody combination therapy application. The therapy includes ambavirumab injection (BRII-196) and rotavirumab injection (BRII-198). These two drugs can be used in combination to treat mild and common types with progression to severe (Including hospitalization or death) adults and adolescents (12-17 years old, weight ≥40 kg) with high-risk factors (COVID-19) patients.

At the beginning of last year, Tengsheng Biopharmaceuticals Biotechnology Co., Ltd. (hereinafter referred to as ) and Tsinghua University and Shenzhen Third People’s Hospital jointly established Develop new coronavirus neutralizing antibody drugs. "Ambavirumab/Romisvirimab combination therapy reduces the risk of hospitalization and death of outpatients with high risk of clinical progression of new crown by 80%."Tengsheng Huachuang CEO Luo Yongqing told a reporter from China Business Daily that 837 patients infected with the new crown virus from four continents and six countries were divided into groups that used ambavirumab/rotavirumab combination therapy and used The placebo (normal saline) group was compared, and the experimental test was carried out in a randomized, double-blind controlled manner. As of the 28-day clinical endpoint, the treatment group had zero deaths, while there were nine deaths in the placebo group. In the treatment group, no matter what Subjects who started treatment in the early stage (within 5 days after the onset of symptoms) or at the late stage (within 6-10 days after the onset of symptoms) had a significant reduction in hospitalization and mortality.

The specific drug is How does it work? The new coronavirus enters the human body, combines with human cells and replicates in large numbers, infecting other normal human cells. Neutralizing antibody therapy is to inject drugs into the human body, mimicking the antibody produced by the human immune system_ span4span, combined with the new coronavirus, so that the virus loses the ability to bind to human cells.

antibody drug has been successfully applied to treat diseases such as , AIDS, , and Ebola. The antibodies selected this time are isolated from the serum of recovered patients, and are the two antibodies with the strongest binding and antiviral capabilities. At the same time, the epitopes of the two antibodies that bind to the viral spike glycoprotein are different , It can avoid potential future drug resistance, that is, the escape caused by the mutation of the virus, and it is not easy to produce resistance. Use bioengineering to genetically engineer this pair of antibodies to make it The half-life of is longer. Generally, the half-life of antibodies produced by the human body is about 21 days, and the half-life can be as long as 76 days after modification.This also means that the antibody stays in the blood for a longer time and effective concentration.

"The blood concentration of Ambavirimab/Romisvirimab can inhibit the growth of 90% of the virus 300 times, that is, 9 months after injection, it can still inhibit the growth of 90% of the virus 40 times . The protection of the human body lasts as long as 9 months or even 12 months.” Luo Yongqing said.

Second question: " Omi Keron " after the emergence of specific drugs still work

in the test of the safety of the new crown virus therapy and There are zero deaths, but do patients have side effects after use? Zhang Yao, Chief Medical Officer of Tengsheng Huachuang, told China Business Daily: "During the experimental test, the overall incidence of adverse reactions above grade 3 was 3.8%. The most serious adverse reaction was the aggravation of patients with new coronavirus-related pneumonia. Facts In the above, a randomized double-blind format was used in the experimental testing process, so the subjects did not know what the injection was, and the patients who injected the normal saline reported more adverse reactions than the medication patients. Based on this, we believe that the use of antibodies is It is very safe.”

Luo Yongqing said that the combination therapy of ambavirumab/rotamisvirimab reduces the risk of hospitalization and death of outpatients with high risk of clinical progress by 80%.

It is worth noting that neutralizing antibody is more susceptible to virus mutation. Institute of Microbiology, Chinese Academy of Sciences postdoctoral Shi Rui believes that preventing the failure of neutralizing antibody drugs due to viral mutations is a difficulty in the preclinical development of new crown antiviral drugs.Most neutralizing antibody drugs act on a single site (mostly the receptor binding domain of the S protein on the surface of the virus). If the key amino acid site of the receptor binding domain is mutated during the passage of the virus, the neutralizing antibody drug may Facing failure.

Before the approval of the first domestically produced anti-neovirus specific drug, the "super" mutant strain of the new crown "Omi Keron" was just discovered. Studies have shown that the combination therapy of ambavirimab/romisvirimab is effective against "Alpha", "Beta", "Gamma", "Epsilon", "Delta", "Delta+", "Lambda" and Virus mutants such as "Miao" are effective, but are they effective against "Omi Keron"?

Luo Yongqing said: “When the neutralizing antibody combination therapy was in clinical trials from January to July this year, it was the time when the mutant strain was pandemic. From the earliest'alpha' beta' to ' Virus variants such as Delta', and the neutralizing antibody Ambavirumab/Romisvirumab can remain active. At present, we have four laboratories around the world conducting experiments to determine whether Omi Keron has an effect on Ambar Weirzumab/Romisvirzumab combination therapy has an impact, and the results will be seen in the next two weeks or so. I am confident in the effectiveness of the drug."

Three questions: the future of specific drugs Will it become a "sky-priced drug"?

Li Ankang, Chief Financial Officer of Tengsheng Biopharma, told a reporter from China Business Daily that the current price of a new coronavirus-neutralizing antibody combination therapy needed by a patient in the United States It's $2,100, including two 50ml ambavir monoclonal antibodies and two 50ml romisvirimab. The dose used is "1 gram + 1 gram", which is based on the concentration of the drug distributed in the body to calculate a dose sufficient to attack the virus.

Cold chain transportation , production technology, cost of use... Will the high price become a major "label" after the advent of the first domestically-made anti-coronavirus drug? Take the new crown monoclonal antibody Bamlanivimab of Eli Lilly as an example,The CEO of Eli Lilly has publicly stated that the price of a single Bamlanivimab drug in developed countries will be US$1,250 per bottle per course of treatment, and a tiered pricing model will be adopted according to the country’s ability to pay.

Li Ankang said: "The pricing of the new coronavirus neutralizing antibody combination therapy in the Chinese market has not yet been finalized. We have been communicating and communicating with relevant national departments. The subsequent pricing will be based on government orders and drugs. The supply volume will be determined after further research. In addition, according to the current demand, the production capacity of pharmaceuticals is sufficient. At present, we have entrusted the production of pharmaceuticals to WuXi Biologics, which ranks among the top three in the world and has huge production capacity, so We are not worried about production capacity. In the future, when the scale of production expands, the cost will be reduced. If the production volume increases in the future, there should be room for further reduction in drug prices."

It is worth mentioning that even if there is With the new crown-specific drugs, vaccines are still indispensable. Luo Yongqing said that the new crown vaccine is the active immunization of , but some people may have different levels of antibodies after vaccination. The treatment of new crown specific drugs and the new crown vaccine are complementary to each other. In addition, in terms of prevention, the new crown drug is more suitable for those people whose antibody levels are still low after vaccination, as well as people with cancer, high blood pressure and other diseases and people with low immunity.

"In terms of the prevention of the new coronavirus, neutralizing antibody drugs can only be a supplement to vaccines. Because even in large-scale production, the cost of neutralizing antibody drugs cannot be lower than vaccines. Therefore, for large-scale production, The first choice for prevention is vaccines.” Li Ankang said.

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new crown special drugs behind the market for nearly 100 billion yuan, pointed out that there is a market of nearly 100 billion yuan behind the new crown special drugs _span _sp9 _strongThe commercialization market space of COVID-19 neutralizing antibody drugs can reach US$6.9 billion to US$14.6 billion (approximately RMB 44.8 billion to 94.9 billion). According to statistics, there are currently 217 therapeutic antibody projects against the new coronavirus in the world have entered the development stage, of which three groups of antibody therapies have been granted emergency authorization for use in the treatment of patients infected with the new coronavirus; 79 antibody projects are in clinical trials Medium (Phase I/II/III); 66 antibody projects are in the early detection stage, of which 60 antibody projects are in the preclinical stage; at least 29 countries and 291 companies/institutions are developing antibody therapies against the new coronavirus.