More affordable, this broad-spectrum and effective domestic COVID-19 treatment drug is on its way

In the current grim situation of the pandemic, people are eagerly awaiting the emergence of a miracle drug.

The good news is, currently, two COVID-19 treatment drugs have conditionally been approved for marketing in China. They are Pfizer's COVID-19 treatment drug Paxlovid and Henan True Biotech Technology Co., Ltd.'s Azvudine tablets. Among them, Pfizer's Paxlovid (a combination package of Nirmatrelvir tablets/Ritonavir tablets) works as a 3CL (3C-like protease) protease inhibitor; Azvudine tablets work as an RNA polymerase (RdRp) inhibitor.

In addition, major manufacturers are also accelerating the development of COVID-19 treatment drugs. Including Jiangxi Bio 、 Simcere Pharmaceutical 、 Junshi Biosciences 、 Frontier Biotech , Hisun Pharmaceutical and other innovative companies are conducting research based on their respective technological paths, bringing more possibilities to the future COVID-19 treatment market.

Taking Jiangxi Bio as an example, it is entering through serum therapy, which will bring to the industry a COVID-19 treatment drug that is broad-spectrum, efficient, safe, low-cost, and easy to mass-produce. In other words, this drug is effective against various COVID-19 variants and is more affordable.

It should be noted that, there will be a great demand for COVID-19 treatment drugs for a considerable period ahead. According to an assessment by Founder Securities, China will complete a drug reserve covering 10% of the total population in the next three years, which means about 150 million people will have reserves of oral COVID-19 drugs. Based on this estimate, the procurement volume of COVID-19 treatment drugs from 2023 to 2025 will reach 30 million, 50 million, and 60 million doses respectively, growing rapidly.

Undoubtedly, a race to accelerate the development of COVID-19 treatment drugs is underway.

01 Acceleration of COVID-19 Treatment Drug Development, But Challenges Remain

Recently, the number of positive infections across China has been growing exponentially, and the peak of COVID-19 infections is approaching, posing a serious threat to vulnerable groups with underlying diseases and severe risk factors.

After all, China has a large population with substantial numbers in every age group. According to the seventh national 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 response, the State Council's joint prevention and control mechanism specifically pointed out the need to fully address the urgent and difficult problems faced by the public.

Under these circumstances, stockpiling COVID-19 treatment drugs has become an urgent priority.

From the latest progress, relevant treatment drugs in China are in an accelerated development phase, urgently needing more drugs to be marketed. From a global perspective, the development of COVID-19 treatment drugs is equally urgent. AstraZeneca (AstraZeneca), Regeneron, GlaxoSmithKline (GSK), and Eli Lilly, among other international giants, continue to advance their COVID-19 drug development, with some chemical drugs and monoclonal antibody drugs already on the market.

However, the problem is, anti-COVID-19 drugs currently face significant difficulties, as two types of drugs have certain limitations when dealing with a constantly mutating virus like COVID-19.

The reason behind this is that with the rapid evolution of the COVID-19 virus, different strains have mutations in different locations, which directly affect the drug's therapeutic effect, resulting in a short lifespan for many COVID-19 drugs under development.

Additionally, the dominant position of a variant strain rarely lasts more than a few months — they either evolve into different sub-variants or are replaced by new variants. This has caused many monoclonal antibody drugs authorized for emergency use abroad to be withdrawn due to ineffectiveness against variants.

The two marketed COVID-19 chemical drugs are somewhat unsatisfactory, either due to controversies over toxic side effects, supply shortages, or high prices.

Therefore, the industry urgently needs a drug that has good neutralizing effects against various variants, is affordable, and has sufficient supply.

02 Entering through Serum Therapy: Broad-Spectrum Effective COVID-19 Treatment Drugs Are on the Way

Among the innovative companies developing COVID-19 treatment drugs, 36Kr learned that Jiangxi Institute of Biological Products Co., Ltd. (hereinafter referred to as "Jiangxi Bio") has taken a differentiated path, entering through serum therapy to explore another possibility for COVID-19 treatment drugs.

"Jiangxi Bio is a company with over fifty years of biopharmaceutical history, mainly engaged in the research, production, and sales of antitoxins and immune serum biological products. After the outbreak of the pandemic in 2020, we were very eager to use Jiangxi Bio's own capabilities and R&D system to contribute to the treatment of COVID-19," Jiangxi Bio Chairman Jing Yue told 36Kr. At the early stage of the pandemic, the company closely followed the latest industry developments to quickly start research on anti-COVID-19 virus serum.

To this end, Jiangxi Bio cooperated with Professor Wang Peng's research team at the Southern University of Science and Technology Medical School. After continuous efforts, the two parties developed a deglycosylated viral surface protein (recombinant S protein RBD fragment) antigen for horse immunization. Research shows that glycosylation on the surface of the COVID-19 protein is crucial for immune evasion by the virus. Using deglycosylated antigens can greatly enhance immune effects, producing broader and longer-lasting neutralizing effects.

It is worth mentioning that in tests of neutralizing activity against different COVID-19 variants, the anti-COVID-19 virus serum against live virus (SARS-CoV-2 WT, Delta, Omicron BA.1, BA.2, and BA.5 strains) and pseudoviruses (SARS-CoV-2 WT, Delta, Omicron, Beta, and Alpha) all showed good viral neutralizing activity. (Neutralization data for BA.5 is temporarily withheld as the research results have not yet been published)

Then, after the antibodies were mass-produced, Jiangxi Bio collaborated with infectious disease experts from the Medical School of Southern University of Science and Technology The team led by Professor Li Liang, the advocate of the "urban immune system" concept, worked together with the Shenzhen Center for Disease Control and Prevention to test the efficacy of the antibodies, conducting live virus neutralization experiments using the original strain, Delta strain, Omicron BA.1, BA.2, and BA.5 strains.

"The results showed that the antibodies had very good neutralizing effects against each variant strain, with neutralization rates exceeding 95% for Delta and Omicron BA.2 in respiratory organoids." Jiangxi Bio Chairman Jing Yue stated that the anti-COVID-19 serum (immunoglobulin F(ab)’2 fragment) broad-spectrum neutralizing antibody drug is currently a special drug with neutralization efficiency exceeding 95% against all COVID-19 variants.

In terms of safety, the product has undergone safety studies in mice and crab-eating macaques, testing acute toxicity, in vivo drug metabolism, inflammatory factors, hemolysis, and other safety parameters, with no adverse reactions observed. Currently, the product has completed the production of a 20,000-bottle pilot batch in a cleanroom compliant with GMP management standards, all meeting quality standards, and is currently conducting production of clinical batches and preclinical studies.

Dr. Shen Guangfu, Director of Biotechnology at Jiangxi Bio, told 36Kr: " The anti-COVID-19 serum has characteristics of broad spectrum, high efficiency, safety, low cost, and ease of large-scale production, making it more suitable for treating highly mutable viruses. ”

Despite such excellent therapeutic capabilities, anti-serum is not a new concept. Since Emil von Behring and Shibasaburo Kitasato invented anti-serum in 1890, it has gradually developed rapidly and is now widely used in the prevention and treatment of highly fatal diseases such as tetanus, botulism, snake venom poisoning, and rabies virus infection.

"People generally think that injecting anti-serum easily causes serum sickness or severe allergic reactions, but this was actually because the anti-serum purification technology was relatively backward in the last century, resulting in complex component composition and a very high rate of adverse reactions," Dr. Shen Guangfu said. "Currently, purification technology in the industry has made significant progress, these problems have been well resolved, and the new generation of horse anti-serum products have high neutralization efficiency, no obvious side effects, and can be produced on a large scale at relatively low cost."

Although widely applied, entering the anti-serum industry is not easy due to its high entry barriers. The reason is that research on chemical drugs or monoclonal antibody drugs can be conducted in organic synthesis or biochemical laboratories, but research on anti-serum requires crossing three industries.

How to understand this? We need to go back to the entire preparation process of anti-serum.

Specifically, horse-derived antibodies are antibodies extracted from horse blood after vaccinating the horses. Therefore, to develop a horse-derived antibody, roughly three steps must be completed.

First, the ability to research and prepare antigens is needed; next, thousands of horses must be raised and their health ensured, applying scientific immunization protocols to inject antigens to ensure the horses' immune systems produce a good response, generating plasma containing high-titer neutralizing antibodies. Thus, Jiangxi Bio built the largest immunized horse breeding base in China in Zhangye, Gansu, with a capacity of over ten thousand horses; finally, the required antibodies must be extracted in a modern protein purification workshop.

It can be seen that anti-serum research spans the vaccine, breeding, and antibody drug industries. This requires not only comprehensive technical capabilities but also excellent enterprise coordination and management skills.

"Based on our accumulation in the anti-serum field, we want to build a rapid drug response platform for infectious diseases centered on the 'polyclonal antibodies' in horse anti-serum. What does this mean? For example, when we come into contact with and are infected by various pathogens, the body produces immune memory and generates immune cells and antibodies. The next time we encounter such viruses, we can fight them off," said Professor Li Liang, a cooperating expert of Jiangxi Bio. "Through this approach, we can build an immune system for the city, study all possible troublesome infectious diseases, and reserve related vaccine and antibody candidate drugs."

The benefit is that once an infectious disease outbreak occurs, people can quickly respond and adapt. The characteristics of polyclonal antibody drugs are suitable for rapid drug development and treatment of sudden major infectious disease epidemics, forming a complete industrial chain that can effectively ensure regional biosafety. Artificially constructing an urban immune system is crucial for building a biologically safe and resilient city.

It is not difficult to see that by starting from serum therapy, Jiangxi Bio has found another possibility for COVID-19 treatment drugs and provided ideas for subsequently building a rapid drug response platform to create a biologically safe and resilient city.

03 Innovation Drives Company Development Social Responsibility Is an Unchanging Foundation

For an innovation-driven company, research and development strength is fundamental to its development.

To this end, Jiangxi Bio currently has four subsidiaries: Hainan Pharmaceutical Research Institute (commissioned drug testing and research), Jiangsheng (Shenzhen) Biotechnology R&D Center (frontier science and technology research), Chifeng Boen Pharmaceutical (research, production, and sales of veterinary drugs, including biological and chemical drugs), and Gaotai Tianhong Biochemical (immune plasma production and horse breeding and raising).

As a leading national anti-serum enterprise, Jiangxi Bio is also one of China's largest tetanus antitoxin (TAT) manufacturers, with an annual output exceeding 40 million bottles, occupying more than 60% of the domestic TAT market share and 95% of China's TAT export share. Its products are sold to more than 30 countries overseas. The development of this COVID-19 treatment drug has further demonstrated Jiangxi Bio's technological R&D strength in the industry.

However, in Jing Yue's view, practicing social responsibility has always been an unchanging foundation for Jiangxi Bio.

Currently, the prices of newly launched COVID-19 treatment drugs are generally quite expensive. For example, Pfizer's Taking Paxlovid (Nirmatrelvir/Ritonavir combination pack) as an example, its price on internet medical platforms is 2980 yuan per box. The price of monoclonal antibody drugs is even higher, often reaching thousands to tens of thousands. This places a considerable burden on patients and the healthcare system.

Jiangxi Bio aims to break this situation and make the price of COVID-19 treatment drugs more affordable. How to achieve this? We need to look at the cost structure of the drugs.

First, the main costs of a new drug lie in two aspects: one is R&D costs, and the other is manufacturing costs, with the core being the former. It is well known that in the field of new drug development, there is the "Rule of Tens," which states that developing a new drug takes more than 10 years and costs 1 billion USD, with only about 10% of new drugs being approved for clinical trials. But this mainly applies to traditional small molecule drugs.

"Our multi-antibody formulations have an average R&D time of 2-5 years and average R&D costs that are 1/10 to 1/100 of other drug routes," said Jing Yue, Chairman of Jiangxi Bio. The project has a 100% success rate from research start to preclinical study entry, greatly reducing R&D costs and allowing drug prices to be controlled within a reasonable range once marketed, thus providing affordable medicine to the public.

Besides affordable drug prices, Jiangxi Bio has also maintained a consistent habit of fulfilling social responsibilities for decades, such as donating to education and rural poverty alleviation. Recently, Jiangxi Bio donated nucleic acid test kits and nucleic acid testing instruments worth over 1 million yuan of scarce anti-epidemic materials to Cuba through the Shenzhen Red Cross, Shenzhen People's Congress, and the Cuban Embassy in Guangzhou.

Of course, for enterprises, the greatest value lies in bringing 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 field of anti-serum and will build a rapid response platform for drugs treating major infectious diseases to provide assistance and support for clinical treatment, epidemic prevention and control, disaster relief, 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 development to the successive launch of COVID-19 treatment drugs, the healthcare industry has accelerated innovation, providing the greatest support to safeguard people's life and health.

Taking COVID-19 drugs as an example, the development of related drugs in China has now entered a flourishing stage, with corresponding drugs for COVID-19 prevention, treatment of mild to moderate cases, and treatment of severe cases all in place, expecting 2023 to be a key harvest period.

In this process, those companies with true innovation capabilities that bring the greatest value to society will ultimately receive the most substantial rewards.

 

This article is reprinted from 36KR (Xiaoxi).

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