With a more affordable price, a domestically produced broad-spectrum effective COVID-19 treatment drug is on its way.

In the current unfavorable epidemic situation, people are eagerly awaiting the emergence of effective drugs.

The good news is, Two COVID-19 treatment drugs have been conditionally approved for marketing in China. ，分别为辉瑞公司新冠病毒治疗药物 Paxlovid, a COVID-19 treatment drug from Pfizer, and Azvudine tablets from Henan Real Biotech Technology Co., Ltd. Specifically, Pfizer's Paxlovid (Nirmatrelvir tablets/Ritonavir tablets combination pack) works as a 3CL (3C-like protease) proteinase inhibitor; Azvudine tablets work as an RNA polymerase (RdRp) inhibitor.

In addition, Major manufacturers are accelerating the research and development of COVID-19 treatment drugs. 。包括 Jiangxi Bio 、 Simcere Pharmaceutical 、 Jun Shi Bio 、 Frontier Biotech and many other innovative enterprises such as Haizheng Pharmaceutical are conducting research based on their own technical paths, creating more possibilities for the future COVID-19 treatment market.

Taking Jiangxi Bio as an example, its entry into serum therapy will bring to the industry broad-spectrum, highly effective, safe, low-cost, and easily mass-produced COVID-19 treatment drugs. In other words, this drug is effective against all types of COVID-19 variants and is more affordable.

It should be noted that, There will be a large demand for COVID-19 treatment drugs for a considerable period of time. According to Fangzheng Securities' assessment, China will complete the drug reserves covering 10% of the total population in the next three years, which means that about 150 million people will have reserves of oral COVID-19 drugs. Based on this calculation, the procurement volume of COVID-19 treatment drugs in 2023-2025 will reach 30 million, 50 million, and 60 million units, respectively, showing rapid growth.

Undoubtedly, an accelerated race in the research and development of COVID-19 treatment drugs is underway.

01 Accelerated Research and Development of COVID-19 Treatment Drugs, but Challenges Remain

Recently, the number of positive infections in various parts of China has increased exponentially, and the peak of COVID-19 infections is approaching, posing a serious threat to vulnerable populations with underlying diseases and severe risk factors.

After all, China has a large population, and the number of people in each age group is very large. According to the results of the seventh national population census, The population aged 0-14 is 250 million, accounting for 17.95%, and the population aged 60 and above is 260 million, reaching 18.7%. In view of this, the State Council's Joint Prevention and Control Mechanism specifically pointed out that it is necessary to make every effort to solve the urgent problems of the masses.

Under this circumstance, reserving COVID-19 treatment drugs has become an urgent task.

From the latest progress, China's relevant treatment drugs are in the accelerated research and development stage, and more drugs are urgently needed to be put on the market. From a global perspective, the research and development of COVID-19 treatment drugs is equally urgent. AstraZeneca (AstraZeneca), Regeneron, GSK, and Eli Lilly and other international giants are also continuously advancing the research and development of COVID-19 drugs, and some chemical drugs and monoclonal antibody drugs have been launched.

However, the problem is that, Anti-COVID-19 drugs are currently facing considerable difficulties, that is, the two drugs have certain limitations in dealing with constantly mutating viruses like COVID-19.

The underlying reason is that, with the rapid evolution of the COVID-19 virus, different strains, due to different mutation sites, will directly affect the therapeutic effect of the drug, resulting in a very short lifespan for many COVID-19 research and development drugs.

In addition, the dominant position of a general variant strain rarely lasts more than a few months —they will either evolve further into different sub-variants, or they will be replaced by new variants. This has led to the delisting of many monoclonal antibody drugs that have been launched through emergency authorization abroad because they are ineffective against mutant strains.

As for the two COVID-19 chemical drugs that have been launched, they are somewhat unsatisfactory, either due to controversy over toxicity and side effects, or due to insufficient supply and high Price.

Therefore, the industry urgently needs a drug that has a good neutralizing effect on all types of mutant strains, is affordable, and has sufficient supply.

02 Entering from Serum Therapy, Broad-spectrum Effective COVID-19 Treatment Drugs are on the Way

Among the innovative enterprises in the research and development of COVID-19 treatment drugs, 36Kr learned that Jiangxi Bio Products Research Institute Co., Ltd. (hereinafter referred to as "Jiangxi Bio") has taken a differentiated path, that is, Entering from serum therapy to explore another possibility for COVID-19 treatment drugs.

“Jiangxi Bio is an enterprise with more than 50 years of history in biopharmaceutical manufacturing, mainly engaged in the research, production and sales of antitoxins and immune serum biological products. After the outbreak of the epidemic in 2020, we really hope to use Jiangxi Bio’s own capabilities and R&D system to contribute to the treatment of the COVID-19 epidemic.” Jing Yue, chairman of Jiangxi Bio, told 36Kr that at the beginning of the epidemic, the company has been paying close attention to the latest progress of the industry in order to carry out research on anti-COVID-19 serum as soon as possible.

To this end, Jiangxi Bio launched a cooperation with Professor Wang Peng’s research team at Southern University of Science and Technology Medical College. After continuous efforts, both sides developed a deglycosylated viral surface protein (recombinant S protein RBD fragment) antigen with good immunogenicity for equine immunization. Studies have shown that glycosylation of the surface of the COVID-19 protein is crucial for the virus’s immune escape, and the use of deglycosylated antigens can greatly improve the immune effect, producing a more broad-spectrum and lasting neutralizing effect.

It is worth mentioning that, in the test of neutralizing activity against different COVID-19 variants, the anti-COVID-19 serum against live viruses The SARS-CoV-2 WT, Delta, Omicron BA.1, BA.2, and BA.5 strains and pseudotyped viruses (SARS-CoV-2 WT, Delta, Omicron, Beta, and Alpha) all showed good neutralizing activity. (Neutralization data for BA.5 is temporarily withheld due to unpublished research findings).

Following mass production of the antibody, Jiangxi Bio also collaborated with Professor Li Liang's team, infectious disease experts from the Southern University of Science and Technology Medical College and advocates of the "urban immune system" concept, and the Shenzhen Center for Disease Control and Prevention to test the antibody's efficacy. Neutralization experiments using live viruses were conducted with the original strain, Delta strain, Omicron BA.1, BA.2, and BA.5 strains. “The results showed that the antibody had a good neutralizing effect on each variant, achieving more than 95% neutralization of Delta and Omicron BA.2 in respiratory organoids.” Jiangxi Bio chairman Jing Yue stated that the anti-SARS-CoV-2 serum (immunoglobulin F(ab)’2 fragment) broad-spectrum neutralizing antibody drug is a highly effective drug with a neutralization efficiency of over 95% against all currently known SARS-CoV-2 variants.

In terms of safety, safety studies have been conducted in mice and cynomolgus monkeys, testing safety parameters including acute toxicity, in vivo drug metabolism, inflammatory factors, and hemolysis, with no adverse reactions observed. Currently, 20,000 bottles of the product have been produced in a GMP-compliant cleanroom, meeting quality standards, and clinical batch production and pre-clinical research are underway.

In terms of safety, the product has undergone safety research in mice and cynomolgus monkeys, testing items such as acute toxicity, in vivo drug metabolism, inflammatory factors, and hemolysis, all without any observed adverse reactions. Currently, the product is undergoing production of clinical batches and pre-clinical research in a cleanroom compliant with GMP standards. In a cleanroom that meets Good Manufacturing Practice (GMP) standards, a pilot batch of 20,000 bottles of the product has been completed, all meeting quality standards. Clinical batch production and pre-clinical research are currently underway.

Dr. Shen Guangfu, the chief technology officer of Jiangxi Bio, told 36Kr: " The anti-SARS-CoV-2 serum has the characteristics of broad spectrum, high efficiency, safety, low cost, and ease of mass production, making it more suitable for the treatment of highly mutable viruses. ”

Despite its impressive therapeutic capabilities, antiserum is not a novel development. Since the invention of antiserum by Emil von Behring and Shibasaburo Kitasato in 1890, antiserum has rapidly advanced and is now widely used in the prevention and treatment of highly lethal diseases such as tetanus, botulism, snake venom poisoning, and rabies.

“People generally believe that injecting antiserum can easily cause serum sickness or severe allergic reactions, but this is actually because the purification technology of antiserum in the last century was relatively backward, resulting in complex composition and a very high rate of adverse reactions.” Dr. Shen Guangfu said that the industry's purification technology has made significant progress, these problems have been well solved, and the new generation of equine antiserum products have high neutralization efficiency, no obvious side effects, and can be mass-produced at a lower cost.

Despite its wide use, entering the antiserum industry is not easy, as there are high barriers to entry. This is because research on chemical drugs or monoclonal antibodies can be carried out in organic synthesis or biochemical laboratories, but research on antiserum requires crossing three industries.

What does this mean? This needs to be explained in the context of the entire antiserum preparation process.

Specifically, equine antibodies are extracted from the blood of horses after vaccination. Therefore, to develop an equine antibody, three steps must be followed.

First, the ability to research and prepare antigens is needed; then, thousands of horses need to be raised, and their health must be ensured, using scientific immunization procedures to inject antigens, ensuring that the horses' immune systems produce a good response, producing plasma containing high-titer neutralizing antibodies. Jiangxi Bio has therefore built China's largest-scale equine breeding base in Zhangye, Gansu, with a breeding capacity of over 10,000 horses; finally, the required antibodies need to be extracted in a modern protein purification workshop.

In short, antiserum research spans the vaccine, animal husbandry, and antibody drug industries. This requires not only comprehensive technical capabilities but also the company's excellent overall management capabilities.

“Relying on our accumulation in the field of antiserum, we want to build a rapid response platform for infectious diseases based on ‘polyclonal antibodies’ in equine antiserum. What does this mean? For example, after we come into contact with and are infected by various pathogens, our bodies will produce immune memory and produce immune cells and antibodies. Next time we encounter this kind of virus, we can deal with it,” said Professor Li Liang, Jiangxi Bio's collaborating expert. “In this way, we can create an immune system for the city, studying all the infectious diseases that may cause trouble and reserve related vaccines and antibody candidate drugs.”

This results in the ability to respond quickly to outbreaks of infectious diseases. The characteristics of polyclonal antibodies are suitable for the rapid development and treatment of major emerging infectious diseases, forming a complete industrial chain, effectively ensuring regional biosecurity, artificially building the city's immune system, and playing a vital role in building a biosecure resilient city.

It is not difficult to see that by entering the serum therapy field, Jiangxi Bio has found another possibility for the treatment of COVID-19 and provided a way of thinking for building a biosecure resilient city through the construction of a rapid drug response platform.

03 Innovation Drives Company Development; Social Responsibility is the Unchanging Foundation

For an innovation-driven company, R&D capabilities are fundamental to its development.

To this end, Jiangxi Bio currently has four subsidiary companies: Hainan Pharmaceutical Research Institute (commissioned testing and research of pharmaceuticals), Jiangsheng (Shenzhen) Biotechnology R&D Center (research on cutting-edge science and technology), Chifeng Boen Pharmaceutical Co., Ltd. (R&D, production, and sales of veterinary drugs, including Chinese herbal medicine and chemical drugs), and Gaotang Tianhong Biochemical (immune plasma production and horse breeding and raising).

As a leading antiserum company in China, Jiangxi Bio is also one of the largest manufacturers of tetanus antitoxin ( TAT) in China, with an annual output of more than 40 million bottles, accounting for more than 60% of the domestic TAT market share and 95% of China's TAT export share. Products are exported to more than 30 countries worldwide. The development of this COVID-19 treatment further showcases Jiangxi Bio's technological R&D capabilities.

However, in Jing Yue's view, the practice of social responsibility has always been the unchanging foundation of Jiangxi Bio.

Judging from the currently available COVID-19 treatment drugs, the Price is generally quite high. For example, Pfizer's Take Paxlovid (Nirmatrelvir tablets/Ritonavir tablets combination pack) as an example; its price on internet medical platforms is 2980 yuan per box. The price of monoclonal antibody drugs is often in the thousands or tens of thousands. This has placed a considerable burden on patients and the medical system.

Jiangxi Bio wants to break this situation and make the Price of COVID-19 treatment drugs more affordable. How? This requires looking at the cost structure of the drug.

First, the main costs of a new drug fall into two categories: research and development costs and manufacturing costs, with the former being the core. As is well known, in the field of new drug research and development, there is a concept called the “double ten law”, which means that the research and development of a new drug requires more than 10 years and 1 billion US dollars in costs to be successfully developed, and only about 10% of new drugs can be approved to Enter the clinical phase. However, this mainly applies to traditional small molecule drugs.

“The average research and development time for our multi-antigen preparations is 2-5 years, and the average research and development cost is 1/10 to 1/100 of other drug routes,” said Jing Yue, chairman of Jiangxi Bio. The success rate of the project from research to pre-clinical studies is 100%, which greatly reduces research and development costs, so that once the drug is on the market, the Price can be controlled within a certain reasonable range, thereby providing affordable drugs for the public.

In addition to affordable drug Prices, Jiangxi Bio has maintained its decades-long habit of practicing social responsibility. For example, donations to support education and poverty alleviation in rural areas. Recently, Jiangxi Bio, through the Shenzhen Red Cross Society, Shenzhen People’s Congress, and the Cuban Embassy in Guangzhou, donated nucleic acid testing reagents and nucleic acid testing instruments worth over 1 million yuan in scarce anti-epidemic materials.

Of course, for enterprises, the greatest value is to bring more and better solutions to society and the market through their own innovation and products. Facing future development, Jiangxi Bio will continue to focus on the antiserum field, and will build a rapid response platform for drugs used to treat major infectious diseases to provide assistance and support for clinical treatment, epidemic prevention and control, disaster relief, etc., and continuously produce innovative pharmaceutical products needed by patients and the industry.

In the three years since the outbreak of COVID-19, from nucleic acid testing and vaccine research and development to the gradual listing of COVID-19 treatment drugs, the medical and health industry has achieved an accelerated innovation, thereby providing maximum support for ensuring people’s life safety and health.

Taking COVID-19 drugs as an example, China’s related drug development has now entered a state of blooming, with corresponding drug layouts for COVID-19 prevention, treatment of mild and moderate patients, and treatment of severe patients. It is expected that 2023 will be a key harvest year.

In this process, those companies that truly have innovation capabilities and bring the greatest value to society will ultimately receive the richest rewards.

 

This article is reprinted from a 36KR.com (Xiao Xi) article.

Original link Address: https://36kr.com/p/2065210205912194?channel=wechat