Frost & Sullivan officially releases the '2025 Independent Market Study on the Innovative Biopharmaceutical Industry' | Innovative biopharmaceuticals drive the in-depth development of the biopharmaceutical industry

Biopharmaceuticals, also known as biological products, refer to bioactive preparations made from microorganisms, parasites, animal toxins, biological tissues as starting materials, using biological processes or separation and purification techniques, and controlling the quality of intermediate products and finished products through biological and analytical techniques.

Biologics can be divided into recombinant protein drugs (including peptide hormones, cytokines, enzymes, etc.), antibody drugs (including monoclonal antibodies, human immunoglobulins, multispecific antibodies, antibody conjugates, and antibody fusion proteins), cell-based drugs (including stem cell drugs, immune cell drugs, etc.), and other types of biologics.

The market scale of biopharmaceuticals in China has grown from 262.2 billion yuan in 2018 to 534.8 billion yuan in 2024, with an annual compound growth rate of 12.61%. Based on academic research and years of R&D investment, the biopharmaceutical market has developed rapidly in recent years, especially in the prevention and treatment of chronic diseases, where it has shown ideal results and gradually become a routine prevention and treatment method. With continuous investment in innovative research and development, the development of innovative biopharmaceutical preparation processes, the follow-up of biosimilars, and with the support of relevant policies, the Chinese biopharmaceutical market will maintain a rapid growth trend. It is estimated that by 2028 and 2032, the market scale of biopharmaceuticals in China will grow to 830.8 billion yuan and 1126.8 billion yuan, with annual compound growth rates of 11.64% and 7.92% respectively.

In recent years, China has issued a series of policies to encourage the development of the pharmaceutical industry and biopharmaceuticals, including encouraging innovative drug research and development, simplifying the drug marketing process, broadening the qualifications for marketing authorization holders, strengthening drug safety management, and encouraging the research and development and marketing of rare diseases and orphan drugs.

In the field of biopharmaceuticals, relevant Chinese departments attach great importance to the development of biotechnology and have included it in the 'Healthy China 2030' plan outline. In the field of biopharmaceuticals and antibody drugs, in recent years, the development of domestic and international biopharmaceuticals has shown preferential therapeutic effects in clinical treatment. The proportion included in medical insurance directories has gradually expanded, playing an important role in China's future goals of improving residents' health and hygiene levels, perfecting treatment and health services, and enhancing the treatment effectiveness of major diseases.

Monoclonal Antibodies (mABs) are highly homogeneous antibodies produced by a single B lymphocyte clone that specifically target specific antigenic epitopes. Monoclonal antibodies are characterized by a single active form and strong specificity for antigen binding. Traditional monoclonal antibody drugs possess a complete antibody structure, including antigen-binding fragments (Fab) that determine antibody specificity and affinity, as well as crystallizable fragments (Fc) that induce antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

Based on the degree of humanization of monoclonal antibodies, they can be classified into murine monoclonal antibodies, human-mouse chimeric monoclonal antibodies, humanized monoclonal antibodies, and fully human monoclonal antibodies.

Köhler and Milstein first proposed the method of producing monoclonal antibodies using hybridoma cells in 1975, providing an important tool and approach for immunological research as well as medical treatment of cancer and autoimmune diseases over the following half century. The world's first therapeutic monoclonal antibody drug, molybdenumomab, was marketed in the United States in 1986.

The iterative process of monoclonal antibody drugs has gone through murine monoclonals, human-mouse chimeric monoclonals, humanized monoclonals, and fully human monoclonals. The mainstream technologies for fully human monoclonals include three types: transgenic mouse technology, phage display library technology, and humanized B-cell technology; fully human monoclonals based on human B-cells are also known as natural fully human monoclonals.

The immunogenicity of monoclonal antibody drugs is caused by anti-drug antibodies (ADA) produced by the patient's body, which can affect the efficacy and safety of monoclonal drugs to varying degrees. Monoclonals are classified into murine monoclonals, human-mouse chimeric monoclonals, humanized monoclonals, and fully human monoclonals based on the degree of humanization, with a certain correlation between classification and immunogenicity. Hwang et al. (2005) divided anti-antibody reactions (AAR) into three levels according to patient incidence: negligible (less than 2%), tolerable (2%-15%), and significant (more than 15%). A negligible anti-antibody reaction represents an ideal safety state; a tolerable anti-antibody reaction implies potential risks even if approved for use in malignant or life-threatening diseases; while a significant anti-antibody reaction usually indicates clinical application failure.

Chimerization technology has greatly reduced the immunogenicity of therapeutic monoclonal antibodies, and humanized monoclonal antibodies have further reduced immunogenicity, proving the necessity of iterative updates in antibody humanization. In fully human monoclonal antibodies, the incidence of ADA reactions in fully human monoclonal antibodies based on human single B-cell technology is lower than in those based on transgenic mice and display library technology. However, since there are fewer approved drugs based on the former, more clinical trial data are needed to further verify the differences in the incidence of ADA reactions in fully human monoclonal antibody drugs under different technical approaches.

The market for monoclonal antibody drugs in China is still in its infancy. Many overseas-listed monoclonal antibody drugs have not been approved in China. Additionally, due to their high cost, monoclonal antibody drugs are less accessible to many patients with limited affordability. The market size of monoclonal antibodies in China is expected to reach approximately 131.5 billion yuan in 2024, with a compound growth rate of 42.05% from 2018 to 2024.

With the advancement of biopharmaceutical technology in China in the future, the indications for monoclonal antibody (mAb) drugs in disease prevention and treatment fields will expand. The introduction of innovative mAb drugs will benefit more patients. Additionally, the inclusion of mAb drugs in the national medical insurance catalog and the increase in per capita disposable income will enhance the market penetration rate of mAb drugs. The market scale of mAb drugs in China is expected to increase by 20.17% annually to reach 274.2 billion yuan in 2028 and by 11.39% annually to reach 422 billion yuan in 2032.

Currently, the preparation of fully human monoclonal antibodies highly relies on antibody technology platforms. Establishing a mature antibody technology platform requires a significant amount of time and strict requirements for core technologies, processes, and parameters. Commercially available fully human monoclonal antibodies on the market are mainly derived from the limited antibody technology platforms available today. For example, the XenoMouse platform of Amgen (representing the drug panitumumab), the HuMabMouse platform of BMS (representing the drugs ipilimumab and nivolumab), the RTM platform of Neurimmune (representing the drug aducanumab), and the AIMSelect platform of AIMM (representing the drug nirsevimab). These antibody technology platforms all have high technical barriers, and the advancement of antibody discovery technology determines the high threshold for market entry into monoclonal antibody drugs. Companies with their own antibody technology platforms (such as Heptaresis Pharmaceuticals, Bio-TheraSolutions, etc.) have the potential competitive advantage of reducing R&D costs and increasing the success rate of antibody R&D. In addition, the production of chemical drugs mainly involves direct preparation and synthesis of compounds, without the need to rely on bioproduction systems. Unlike chemical drugs, the production of biopharmaceuticals represented by monoclonal antibody drugs also highly depends on the construction of cell lines. Cell lines are the expression basis for biopharmaceuticals, and biopharmaceuticals under different expression systems have different activities and application scenarios. A mature cell expression system is an important technology for monoclonal antibody drug production and has high technical barriers. For competitors entering the market later, they face high antibody platform technical barriers and bioproduction system technical barriers, which require time and capital for technological breakthroughs.

●Encouraging policies at the national level have emerged frequently, contributing to the vigorous development of the monoclonal antibody market.

In 2021, departments such as the National People's Congress, the National Healthcare Security Administration, and the National Health Commission all proposed to strengthen original and leading scientific and technological research in the 14th Five-Year Plan: Biopharmaceutical technology innovation and antibody drug development were listed as frontier areas of scientific and technological research. Innovative biopharmaceuticals should focus on the field of antibody drugs, with a particular emphasis on developing new antibody drugs for viral infections, tumors, immune diseases, and other conditions. Additionally, policies such as the 'Procedures for the Review of Breakthrough Therapeutic Drugs (Trial)' have encouraged biomedical enterprises to research and create drugs with significant clinical advantages. Drugs like camrelizumab and sintilimab have gradually become blockbuster drugs in the Chinese monoclonal antibody drug market by being included in the category of breakthrough therapeutic drugs.

●The indication area should explore new avenues, with numerous opportunities in the field of infectious or infectious diseases.

Currently, the development of monoclonal antibody drugs globally mainly focuses on the treatment of autoimmune diseases and cancer. There are relatively few monoclonal antibody products that have been commercialized for infectious or contagious diseases globally. Representative drugs include Nirsevimab, jointly developed by AstraZeneca and Sanofi for the prevention of neonatal respiratory syncytial virus, and Omuvimab, an anti-rabies monoclonal antibody developed by North China Pharmaceutical. Compared with the highly homologous competition in the autoimmune disease and cancer treatment tracks, there are currently fewer competitors in the infectious or contagious disease market, offering numerous market opportunities and great development potential. Based on this, biopharmaceutical companies can explore new paths, combine their own expertise and unique advantages, and focus on the research and development of First-in-Class and Me Better innovative drugs in the field of infectious or contagious diseases.

●The immunogenicity issues of monoclonal antibody drugs have not been well resolved, and antibody drugs truly derived from 'human' sources may be favored by the market.

Monoclonal antibody drugs have undergone an iterative process from murine monoclonals to fully human monoclonals, achieving significant success in the pharmaceutical field. Although the immunogenicity of monoclonals has been significantly reduced during this process, the safety of antibody drugs remains a focal point of concern. In the future, antibody development technology may no longer rely on transgenic animals and phage display libraries, but instead directly isolate cells from humans that have been immunized against pathogens or vaccines, encode specific antibody genes into suitable cell lines, and prepare truly 'human' monoclonal antibodies, minimizing antibody immunogenicity and enhancing safety. In 2021, the world's first natural fully human monoclonal Aducanumab was approved by the FDA in the United States for the treatment of Alzheimer's disease, laying the foundation for the development of natural fully human monoclonal antibodies. Natural fully human monoclonal antibody drugs will embrace valuable development opportunities.

●Restricted by the requirements of China's hospital drug management, innovative drugs such as monoclonal antibodies face resistance in entering public hospitals.

Due to the fixed requirement for the variety of drugs equipped by public hospitals, hospitals that have fully stocked their inventory need to remove an equal amount of drugs, creating resistance to innovative monoclonal antibody drugs entering public hospitals. Currently, public hospitals are the largest users of innovative drugs in China. However, affected by policies such as 'zero mark-up rate,' 'drug proportion,' and 'average cost per visit,' monoclonal antibody drugs with higher average treatment costs still face the challenge of slow penetration into various levels of public hospitals after the national medical insurance negotiations have reduced prices.

●Insufficient patient affordability may become a challenge to the development of monoclonal antibody drugs.

In cancer treatment, monoclonal antibodies are often combined with other therapies. For example, trastuzumab combined with pyrotinib and chemotherapy is used for the treatment of HER-positive advanced breast cancer patients, and combination therapy further increases the economic burden on patients. In the prevention or treatment of infectious and contagious diseases, the treatment cost of monoclonal antibody therapy is significantly higher than existing treatment methods. For instance, the unit price of omicizumab (approved for the prevention of rabies) (598 yuan per vial) is higher than that of rabies human immunoglobulin (about 190 yuan per vial). In the underserved market, some patients may not be able to afford the high treatment costs and thus choose clinically downgraded treatment regimens, which is a major obstacle to the popularization of monoclonal antibody drugs.

●The booming development of the vaccine industry may pose a potential threat to the monoclonal antibody drug market.

In recent years, the introduction of blockbuster vaccines such as HPV vaccines and VZV vaccines has driven the development of the vaccine industry in China during the COVID-19 pandemic vaccination campaign and potentially increased residents' awareness of vaccines. In the field of infectious and communicable diseases, residents who receive active immunization vaccines can provide protection similar to that of passive immunization with monoclonal antibodies. For example, if residents have received a full course of rabies vaccine before being bitten by a cat or dog, they do not need to use rabies antiserum again. The increase in vaccine coverage may reduce the potential applicable population for corresponding indications, and how the monoclonal antibody industry responds to the squeeze from the vaccine industry is a challenge that needs to be faced.

The change in demand for tetanus passive immunization preparations is the result of multifaceted social behaviors and activities. With the development of infrastructure construction in China, the potential risk of tetanus exposure for workers engaged in infrastructure projects such as housing, commercial buildings, highways, railways, and power grids may increase; on the other hand, with the development of China's agriculture, forestry, animal husbandry industry, the potential risk of tetanus exposure for workers engaged in social production activities such as grain production, field labor, tree planting, forestry protection, and poultry and livestock breeding may increase during labor. Due to the impact of the Omicron variant of the COVID-19 pandemic in China in 2022, the control measures across the country have become stricter compared to 2021. The reduction in social activities has led to a decrease in the number of residents engaged in social activities, thereby reducing the potential risk of tetanus exposure. As the pandemic gradually stabilizes and is controlled, future social activities such as infrastructure, real estate, agriculture, forestry, and animal husbandry will gradually resume. The recovery of social activities will increase the potential risk of tetanus exposure and raise the demand for tetanus passive immunization preparations.

The clinical manifestations of RSV infection vary greatly. In children, infections can present as mild upper respiratory tract infections or otitis media, or as severe lower respiratory tract infections (Lower Respiratory Tract Infections, LRTI). Clinical manifestations are related to the child's age, underlying diseases, environmental exposure factors, and previous respiratory infection history. In adults, infections can have a variety of clinical manifestations, ranging in severity from mild respiratory symptoms to severe lower respiratory tract infections. 1) Most early RSV infections in children are limited to the upper respiratory tract, clinically presenting as symptoms of upper respiratory irritation such as nasal congestion, runny nose, coughing, and hoarseness. 2) Children with RSV infections can develop into lower respiratory tract infections, mainly manifested as bronchiolitis or pneumonia.

Premature infants account for about 9-12% of newborns. Affected by the continuous decline in China's neonatal birth rate, the number of infants and young children aged 0-1 year has been showing a downward trend year by year. It is estimated that the total number will decrease to 9.311 million and 9.135 million respectively in 2028 and 2032, with annual compound growth rates of -0.46% and -0.47%.