China finally has its own domestic new crown special drug, and this special drug is effective against "Omi Kerong"!
Recently, the official website of the State Drug Administration shows that the new coronavirus neutralizing antibody combination treatment drugs amphavir monoclonal antibody injection (BRII-196) and romizumab injection (BRII-198) developed by Tengsheng Huachuang Pharmaceutical Technology (Beijing) Co., Ltd. have obtained emergency approval and are allowed to be listed.
△ The picture is from People's Vision
These two drugs can be used in combination to treat adult and adolescent patients with novel coronavirus infection in mild and ordinary types with high-risk factors for progression to severe (including hospitalization or death). Among them, the adolescent indication population is conditionally approved.
Prior to this, a total of three NEW CROWN neutralizing antibody drugs around the world were authorized for emergency use by the US FDA, from the combination of Regeneration Yuan, Eli Lilly and Junshi, as well as the combination of GlaxoSmithKline and VIR, all dominated by multinational pharmaceutical giants. This is China's first approved independent intellectual property rights of the new crown virus neutralizing antibody combination treatment drug.
"We are pleased to achieve this important milestone. As a nascent multinational biotechnology company operating in both China and the United States, we are working hard to promote access to this combination therapy for COVID-19 patients in China, meet the needs of drugs for the prevention and control of the new crown epidemic in China, and provide an important tool for scientific response to the complex and changeable new crown epidemic. Tengsheng Huachuang CEO Luo Yongqing said.
Do not lose the efficacy of multinational pharmaceutical companies
Neutralizing antibody refers to a soluble protein that is automatically produced by human immune cells when the virus invades, and it can bind to the antigen on the surface of the virus, thereby preventing the virus from invading the cell.
The new crown neutralizing antibody developed by Tengsheng Huachuang adopts this technical route. This pair of combinations, known as amphavir maclizumab and romizumab, are extracted from the plasma of people who have recovered from COVID-19 infection and synthesized through bioengineering techniques such as genetic modification, increasing their concentration and retention time in the human body. When it is transfused back into the body of a new crown infected person, it can inhibit the spread of the virus for a short period of time.
Due to the design of a pair of antibodies, the combination of amphavir monoclonal antibody/romimab minimizes off-target due to viral variation. According to the data detected by the in vitro chimeric virus experiment, the therapy can maintain neutral activity against the main strains of the new crown virus that are widely concerned, including "Omi Kerong", "Delta", "Delta+", and other highly harmful "Ramda" and "Miao" variant strains.
In particular, according to data from multiple independent laboratories, the combination of amphavir monoclonal antibody/romizumab remains neutral in activity against the new coronavirus variant "Omiqueron". As soon as the news came out, it immediately attracted the attention of all sectors of society. The antibody combinations developed by multinational large pharmaceutical companies, such as Eli Lilly (including Junshi's antibodies) and the antibody combinations developed by Regeneration Yuan, have been found to be ineffective against "Omi Kerong".
Even leaving aside the mutant strains, compared with other similar antibody drugs that have been listed overseas, the combination therapy of amphavir monoclonal antibody/romizumab is not inferior in clinical trial data.
In the "ACTIV-2" Phase 3 clinical trial supported by the National Institutes of Health, 847 outpatients with COVID-19 at high risk of disease progression were randomly divided into treatment and placebo groups. The results of the 28-day trial showed that patients in the treatment group using amphavir maclonumab/romizumab combined therapy had a statistically significant reduction in hospitalization and mortality compared with the placebo group. And this combination therapy can significantly reduce hospitalization and mortality in patients with 5 days or less of illness or 6 to 10 days of onset. Meanwhile, the treatment group achieved zero deaths within 28 days, compared with 9 deaths in the placebo group. This data fully verifies the effectiveness and safety of this combination therapy.
The patients enrolled in this combination therapy international Phase 3 clinical enrollment are all high-risk groups enrolled in the rapid emergence of global variants from January to July this year, and most of these populations are patients with chronic diseases or immune system diseases, such as diabetes, hypertension, obesity, etc. This also goes some way to proving that this innovative therapy from China has enabled patients with lower immunity who are infected with a strain of the virus to have better treatment benefits.
It is particularly noteworthy that Tengsheng Bo Medicine has made genetic modifications to this pair of antibodies, so that its half-life reaches 2-3 times that of ordinary antibodies, and the effective action time in the body can be as long as 9 months, which undoubtedly provides a good therapeutic effect at the same time, but also provides a basis for prevention. Further research is currently underway to assess the preventive effects of this combination therapy in people with poor vaccine responses. This research is being carried out under the auspices of the Guangzhou laboratory team led by Academician Zhong Nanshan.
In the real world, this antibody combination therapy has also shown very good results. It is reported that since the outbreak of infection cases caused by the "Delta" variant in Shenzhen in May this year, Tengsheng Huachuang has donated nearly 3,000 copies of ampavirinumab/romizumab for clinical treatment. So far, nearly 900 patients in more than 20 cities have received treatment for this combination therapy. The Third People's Hospital of Shenzhen, as a patient admitted to the new crown infection, fully affirmed the clinical benefits of this combination therapy. Shenzhen Third Hospital said that after the patient used this combination therapy, the viral load dropped sharply, and within three days, it quickly faced a negative turn, and the indicators of the immune system quickly recovered.
Make the most scientific decisions under pressure
Behind the eye-catching clinical data is a big gamble by Tengsheng Huachuang to make up for China's public health shortcomings.
There are three main bodies behind Tengsheng Huachuang, namely Tengsheng Bo Pharmaceutical, Tsinghua University and Shenzhen Third People's Hospital. In the process of research and development of neutralizing antibody drugs, the three have a clear division of responsibilities, Tsinghua University is responsible for the early stage of antibody screening, Shenzhen Third People's Hospital provides necessary clinical support, and Tengsheng Bo Pharmaceutical leads the research and development and commercialization of drugs.
Regarding the successful listing of this neutralizing antibody, we often see the brilliance and brilliance in the spotlight after success. But behind this success there are unknown truths and twists and turns.
At the beginning of 2020, when Tengsheng Bo Pharmaceutical was preparing to launch the project of neutralizing antibodies for the new crown, it caused huge controversy within the company. The focus of the controversy is that the project is expected to invest more than 1 billion yuan in two years, almost the entire company's net worth. If it fails, or if the new crown virus suddenly disappears like SARS in the past, not only will the 1 billion yuan be lost, but other projects already carried out by the company will also be affected.
When the company's top management is under pressure to start the project, it can be said that it is a huge financial and human risk. And this startup of less than 100 people has stepped forward in the face of the relentless epidemic and made the most scientific decision that many other large pharmaceutical companies are afraid of. Behind this decision also faces more difficulties. The first is the choice of antibodies. Most of the pharmaceutical companies involved in the research and development of the new crown neutralization antibody only make one antibody for risk considerations, and Tengsheng Bo Pharmaceutical has chosen the design idea of a pair of antibodies from the beginning. This is equivalent to making two new drugs at the same time, and the cost of capital and labor will be doubled. But the advantage is that once the disease mutates, one more antibody equals one more firewall. This was later shown that the design of "cocktail" combination therapies was an extremely wise choice.
Another similar option is the initial dose. According to the usual experience, for insurance considerations, when entering the phase III clinical trial, the initial dose of the drug should be set relatively high, and through the subsequent test, step by step to reduce the dose. For example, in the phase III clinical trial of regeneration yuan, the initial dose was set at 8 grams, and the last way was reduced to 2 grams. Tengsheng Huachuang anchored the dose of 2 grams from the beginning. "This is a very brave decision that saves us a lot of resources and ensures better accessibility when the drug is available." Zhang Yao, chief medical officer of Tengsheng Huachuang, said.
There are many more moments like these. Dr. Hong Zhi, the founder of Tengsheng Bo Pharmaceutical, once said in an interview that although drug research and development only took 18 months, the process was extremely difficult, "the company undertook a lot of pressure, and many decisions were made with tears." ”
Be the guardian of public health
In any case, after winning the first certificate of domestic new crown treatment drugs, Tengsheng Bo Pharmaceutical has come to the spotlight of the biomedical industry.
According to public information, Tengsheng Bo Pharmaceutical was established in December 2017 as a dual headquarters structure between China and the United States, and was listed on the Hong Kong Stock Exchange in July 2021. The company's founder, Dr. Hong Zhi, was a senior vice president of GlaxoSmithKline (GSK) in the field of infectious disease treatment, with more than 25 years of biopharmaceutical experience, and other executives also have a resume of international multinational pharmaceutical companies.
At present, the new crown neutralizing antibody is the only drug approved for marketing by Tengsheng Bo Pharmaceutical. However, from the perspective of research and development pipeline, Tengsheng Bo Medicine has made achievements in anti-infectious diseases and central nervous system diseases, involving hepatitis B, AIDS, multi-drug resistant bacteria, depression and other subdivided disease areas. At present, the company's two products in the field of hepatitis B are in the clinical phase II, and the products for AIDS and multi-drug resistant bacteria for depression are in the first phase of the clinic.
From the perspective of product framework, Tengsheng Bo Pharmaceutical is an alternative pharmaceutical company that is willing to gnaw hard bones. Whether it is hepatitis B, AIDS, multi-drug resistant bacteria in the field of infectious diseases, or depression in the field of the central nervous system, it is a difficult pipeline for drug research and development. Taking hepatitis B as an example, existing hepatitis B drugs can only inhibit the activity of hepatitis B virus, and patients need to take the drug for life. The two hepatitis B products under research by Tengsheng Bo Pharmaceutical are designed to challenge the functional cure of hepatitis B.
"At a time when many multinational pharmaceutical companies are turning to cancer or rare diseases, I hope to think more about solving the disease challenges in public health." Dr. Hong Zhi, founder of Tengsheng Bo Pharmaceutical, said that most of the major events and diseases of public health involve tens of millions, or even hundreds of millions of patients. The mission of Temsex Pharmaceuticals is to find effective solutions to the most common diseases in the world that are currently inadequate or untreatable through extraordinary and bold ideas.
As Temson Bo Pharmaceutical's official website says, "Our mission is to address the most serious public health challenges with breakthrough innovation and insight." The approval of the new crown neutralizing antibody is only the first step in the long march, and I believe that there will be higher peaks in the future, waiting for them to conquer.