The first domestic new crown special drug is effective on Omi kerong, the sooner it is used, the better!

Source of this article: Time Weekly Author: Han Liming

Data from four laboratories around the world, including Columbia University and the U.S. Food and Drug Administration (FDA) independent laboratory, confirm that the combination therapy of ampavirinumab and romizumab maintains neutral activity against the new coronavirus variant strain Omicron.

At the experimental data sharing meeting on the "Omikeron" mutant strain of "Omilon" (hereinafter referred to as the "Sharing Meeting") held on December 21, Dr. Zhu Qing, Senior Vice President of Temexport Pharmaceuticals and Head of the Biopharmaceutical Department, disclosed the above information.

In less than 20 months, the combination of amphavir monoclonal antibody/romizumab was approved for marketing on December 8 this year. This is China's first anti-coronavirus special drug with independent intellectual property rights. The therapy is developed by Tengsheng Bo Medicine (02137. Jointly developed by TENGSHENG Huachuang, a subsidiary of HK, Shenzhen Third People's Hospital and Tsinghua University, it is suitable for the treatment of adult mild and ordinary patients with high risk factors for progression to severe (including hospitalization or death).

On December 18, local time, the World Health Organization (WHO) reported that as of December 16, 89 countries and regions around the world had reported confirmed cases of the Aumechjong variant. In countries and regions where community transmission occurs, the Omikeron strain spreads significantly faster than the Delta strain, with a doubling time of between 1.5 and 3 days. In the face of the menacing Aomi Kerong, the existing new crown special drugs also need to face the challenge.

"According to the current accumulated experience, the new crown virus mutation is very rapid and unpredictable, from the perspective of antibody research and development, the most important thing in the future is to find antibodies for broad-spectrum treatment, and the binding point should be very high in the conservative area, and at the same time, it should be highly active." In addition, the main binding site is currently in the RBD part, and whether other binding sites need to be considered or not is also through further research and optimization. Zhu Qing told the Times Weekly reporter.

Neutralization activity was maintained against Omikeron

According to Zhu Qing, the new crown virus mainly infects human cells by binding to ACE2 on human cells, and causes diseases through cell reproduction. Ampavitomab blocks the binding of the virus to ACE2 at the site where the new coronavirus receptor binds directly to ACE2. Romizumil monoclonal antibody targets another site in the receptor binding region of the new coronavirus that does not bind to ACE2, blocking the reproduction of the virus with different mechanisms of action.

The combination of ambavir maclizumab injection (BRII-196) and romimavir monoclonal antibody injection (BRII-198) is a single intravenous dose of "1 g + 1 g". According to Zhu Qing, after intravenous infusion, the blood antibody concentration increases rapidly, and it can reach 300-400ug/ml within a few hours, seizing the best treatment time.

"The clinical trial patient population, which included delta strain data, received an 80% reduction in hospitalization and mortality within 10 days of onset with an ampavirinumab/romizumab combination therapy." Zhu Qing once again emphasized: "Not only in the early stage of the disease, but also in the late treatment can also be effectively alleviated." ”

Due to the mutation of Omilon, ampavirinumab is somewhat reduced in neutralizing the activity of Omiljun, but at high concentrations it can inhibit more than 90% of the virus. There is no change in the activity of romizumab. Under the requirement of combination of drugs, the neutralization activity of ambavir maclizumab/romizumab on the Omexjong mutant strain was not affected. It is reported that the data for the Omiljung strain comes from in vitro chimeric virus tests, and the activity test in animals is currently being actively carried out.

"The dose administered can effectively neutralize the Omiljung strain, and the highest antibody concentration can reach a thousand-fold inhibition of 50% virus growth and a hundred-fold inhibition of 90% viral growth." In addition, through technical modification, the antibody can be extended to 2-4 times, and the high blood concentration is maintained stably for several weeks (2-4 weeks) after administration, enhancing the ability to neutralize activity. Zhu Qing explained at the sharing meeting.

Luo Yongqing, CEO of Tengsheng Huachuang, believes that due to the strong spread of the mutated strains and the rapid spread speed, medical resources are facing great challenges. According to the experience of clinical trials and Emergency Rescue in China, after infection with the virus, it is necessary to suppress the replication and reproduction of the virus as soon as possible, and the earlier the use of neutralizing antibody combination therapy, the better the effect.

In terms of prevention, according to Zhang Linqi, professor of Tsinghua University School of Medicine and director of the Global Health and Infectious Disease Research Center and AIDS Comprehensive Research Center, who led the research and development, with the support of the Ministry of Science and Technology, academician Zhong Nanshan is currently carrying out clinical research, especially for immunodeficiency patients. From the perspective of the mutual coordination of antibodies and the effect of combined punches, including the time retention characteristics in the body, the preventive effect of the therapy is worth looking forward to. Zhang Linqi also mentioned that the same foreign drug has more than 80% of the preventive effect.

(On the afternoon of December 9, 2021, Tsinghua University held a press conference in Beijing to announce that Professor Zhang Linqi of Tsinghua University led the research and development of China's first anti-new crown virus drug approved for marketing.) The picture shows Zhang Linqi showing a drug sample. Image Source/Visual China)

There are at least 13 projects under research worldwide

At present, there are 5 new crown neutralizing antibody drugs on the market worldwide, of which GlaxoSmithKline (GSK.US) and Vir Biotechnology (Vir Biotechnology, VIR. US) co-researched Sotrovamab, Regenerative Element (REGN.NASDAQ) developed cassirimab/Idizumab, Junshi Bio (688180. SH, 01877.HK) of Ettexpressumab/Bavenibumab has been authorized for emergency use (EUA) by the FDA. AstraZeneca's antibody drug cocktail, AZD7442, has not been approved due to its insignificant therapeutic effect.

Zhu Qing revealed that Tengsheng Bo Pharmaceutical's application for the neutralizing antibody drug EUA to the FDA has entered the final stage of approval. "Follow-up plans are to register in other regions, giving priority to areas where patients are already enrolled in the Phase III trial, including Brazil, Argentina, Mexico and other countries, and are actively preparing for registration in other countries." Luo Yongqing added.

"Since May this year, the company has donated neutralizing antibody treatment drugs for emergency treatment without compensation. After being approved for listing, in accordance with China's regulations, it can only be legally used after production. Luo Yongqing said, "In terms of price, it will be priced by considering the purchase volume and other economic factors." It is reported that the similar antibody drugs listed overseas are mainly government procurement, and the price is about $2100 under the order of millions.

According to the data of the new crown drug research and development tracking report released by Southwest Securities on December 17, at least 13 neutralizing antibody projects around the world are currently in phase III clinical and phase II/III clinical trials. In the first three quarters of 2021, the total sales of COVID-19 neutralizing antibody drugs generated US$5.6 billion, of which regeneration yuan/Roche sales were the largest, accounting for nearly 60% of the overall market.

According to the sharing meeting data, the antibodies of Tengsheng Huachuang and GSK remained active against nearly 10 different globally circulating variants and were not affected in any way. At the same time, GSK/Vir was released through the company's official channels, and in vitro pseudoviruses tests showed efficacy against the Omiljung mutant strain.

Despite the good news of neutralizing antibody drugs, since the product was approved for listing, the stock price of Tengsheng Bo Pharmaceutical has fallen by 20.4%. An analyst from a brokerage who did not want to be named analyzed to the Times Weekly reporter: "In the case of good overall control of the domestic epidemic, there are limitations in the treatment cost and use scenario of neutralizing antibody therapy. Coupled with the FDA's stricter approval of domestic innovative drugs, overseas markets will become more and more difficult. ”