Policy Research Institute page Trends in Clinical Development of New Drugs by Chinese Pharmaceutical Companies

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In November 2019, Brukinsa™ (zanubrutinib), a BTK inhibitor developed by China's BeiGene, for the treatment of mantle cell lymphoma (MCL) with at least one prior therapy, was granted U.S. Food and Drug Administration (FDA) The U.S. Food and Drug Administration (FDA) has granted expedited approval. Chinese pharmaceutical companies have been involved in the manufacture and sale of generic drugs to date, but in recent years they have become more actively involved in new drug development, and as mentioned above, some new drugs are beginning to be approved in the United States. We have conducted a survey on the number of clinical development projects by Chinese pharmaceutical companies and the characteristics of these projects.

Research Methods

The analysis was conducted using Informa's Pharmaprojects®, with trend data for 2019 and earlier and data as of May 2020 for 2020, based on the survey methodology described in Policy Research Institute News No. 44 "Research and Development Status of Small Molecular Drugs and Biopharmaceuticals" *1. To count the new active ingredients that are being developed for new drug launches, we selected small molecule drugs (New Chemical Entity, NCE), synthetic nucleic acids, synthetic peptides, and biopharmaceuticals, and excluded biosimilars, new dosage forms, and fixed-dose combinations from the count. Items developed by Chinese pharmaceutical companies were identified by the nationality of the "Originator "*2*3.

Annual Trends in the Number of Items in Clinical Development

Figure 1 shows the number of clinical development items of new active ingredients developed by Chinese pharmaceutical companies as "Originators" by stage over the 10-year period from 2011 to 2020. The left side of Figure 1 shows the total number of products in clinical development as of 2020, an increase of approximately 25-fold over the past 10 years. On the other hand, not all of them are aiming for global development. As shown in the right side of Fig. 1, 93 of the 614 drugs in clinical development in North America, Europe, or Japan in 2020 are considered to be in global development, which is about 15% of the total number of drugs in clinical development.

Figure 1: Number of products in clinical development by Chinese pharmaceutical companies
Source: Created by the Pharmaceutical Industry Policy Institute based on Pharmaprojects®｜Informa, 2020.

Figure 2 shows the breakdown of countries where clinical development is being conducted. 463 of the 614 products in 2020 (75% of the total) are being developed exclusively in China. Others" include Australia and Singapore. In general, R&D activities for products being developed outside of China were also being conducted in China. As for the development stage, the percentage of Phase II or later products was higher for those being developed in North America, Europe, or Japan, and it is possible that products whose safety has been confirmed are being developed outside of China.

Figure 2: Breakdown of Countries with Clinical Development Activities
Source: Created by the Pharmaceutical Industry Research Institute based on Pharmaprojects®/Informa, 2020

Characteristics of Products Developed Globally

As noted in the previous section, the clinical development of products created by Chinese pharmaceutical companies is mainly conducted in China, and some of them are being developed outside of China. In this section, we will discuss items that are being developed in North America, Europe, or Japan (hereafter referred to as "globally developed products"), and in the next section, we will summarize items that are being developed only in China.

Figure 3 shows the characteristics of globally developed products. The most common drug class*5*6 is anti-tumor agents, accounting for nearly 70% of the total. This was followed by gastrointestinal and metabolic drugs and anti-infectives. In terms of modalities, small molecule drugs accounted for nearly 60% of the total, while biopharmaceuticals such as monoclonal antibodies accounted for about 40%. Among biopharmaceuticals, monoclonal antibodies and other antibody drugs accounted for nearly 70% of sales, while chimeric antigen receptor T-cell (CAR-T) therapies, which are being actively developed in China as described below, accounted for only two products. In addition, most of the monoclonal antibodies (including other antibodies) were immune checkpoint inhibitors that target PD-1/PD-L1 and other targets.

Figure 3: Characteristics of Global Development Products (93 products in 2020)
Source: Created by the Pharmaceutical Industry Policy Institute based on Pharmaprojects®/Informa, 2020

Among these 93 products, 14 products were found to have received special measures such as Orphan Drug designation in the U.S. and Europe, including 6 products that received Breakthrough Therapy designation or Fast Track designation from the FDA and PRIME designation from the EMA (European Medicines Agency). NEUCARDIN® is a recombinant human neuregulin-1 fragment. LCAR-B38M and CT-053 are both CAR-T cell therapies that target B-cell maturation antigen (BCMA), They have received special measures from both the FDA and the EMA. LCAR-B38M is being co-developed with Janssen and is being developed outside China by Janssen as JNJ-4528. albuvirtide in combination with 3-BNC117 has Fast Track status for multidrug-resistant HIV infection. albuvirtide is a synthetic peptide developed by Frontier Biotechnologies that acts as a gp41 antagonist of the HIV envelope, and 3-BNC117 is a neutralizing antibody (monoclonal antibody) against HIV developed by Rockefeller University. HTD-1801 is a novel antiviral agent for the treatment of Primary Sclerosing Cholangitis (PSC) and Non-Alcoholic Steatohepatitis (NASH). Alcoholic Steatohepatitis (NASH). ORIN-1001 has a Fast Track designation for the treatment of relapsed/refractory metastatic breast cancer, again with an unknown mechanism of action.

Table 1: Chinese pharmaceutical companies' products under special regulatory measures overseas (selected products)
Source: Prepared by the Pharmaceutical Industry Policy Institute based on Pharmaprojects®｜Informa, 2020 and information published by each company.

Table 2 summarizes the background of the companies that developed the products listed in Table 1, including their locations and year of establishment. Zensun Shanghai Sci & Tech, CARsgen Therapeutics, and Frontier Biotechnologies have been engaged in drug discovery targeting specific disease areas based on research results from their time at domestic and overseas research institutions. The companies are engaged in drug discovery targeting specific disease areas based on the results of research conducted while working at domestic and overseas research institutions. In the case of Nanjing Legend Biotech, the parent company, GenScript, possesses gene synthesis technology closely related to CAR-T cell therapy development, and the company is considered to be developing its business by utilizing its own technology.

Table 2: Companies that created the products listed in Table 1
Source: National Institute of Health Care Policy, based on information published by each company.

Characteristics of Products Developed Only in China

Figure 4 shows the characteristics of products being developed only in China. As with globally developed products, anti-tumor drugs were the most common, accounting for more than 50% of the total. This is followed by anti-infective agents and gastrointestinal and metabolic drugs. As for anti-infectives, the global outbreak of COVID-19 continues, but there are three vaccines against it, so the data does not seem to indicate a specific increase in 2020.

In terms of modalities, the trend was different from that of global development products, with biopharmaceuticals accounting for more than small molecule drugs. In particular, vaccines and CAR-T cell therapies accounted for a large proportion. As for vaccines, 50 out of 55 vaccines were against infectious diseases, and most of them were antiviral vaccines against influenza, hepatitis viruses, and other viruses.

Figure 4: Characteristics of products developed only in China (463 products in 2020)
Source: Created by the Pharmaceutical Industry Policy Institute based on Pharmaprojects®｜Informa, 2020

CAR-T cell therapy

As indicated in the previous section, a large number of CAR-T cell therapies were developed in China, more than the number of monoclonal antibodies. Especially in the last few years, not only the number of products has increased, but also new companies, mainly start-ups, have entered the market. As shown in Figure 5, the number of clinical development products has continued to increase each year since the first two products and one company were identified as of May 2016. 2020 saw a record increase of 46 products over the previous year, with 11 new companies entering the market. In particular, many companies have established bases in Shanghai, Beijing, and Nanjing, indicating the formation of a bio-cluster.

Figure 5 Number of new CAR-T cell therapy products and new entrants
Source: Created by the National Institute of Biomedical Innovation based on Pharmaprojects®/Informa, 2020

Finally, Figure 6 shows the types of antigens targeted, with CD19 being the most common, followed by TNFRSF17 (B cell maturation antigen: same as BCMA). Although there are several other antigens that target not only blood cancers but also solid tumors, many of them target the same antigens, and although the number itself is increasing, it is expected that the selection of items will be progressed to some extent as the development progresses in the future.

Fig. 6 Types of target antigens and number of products
Source: Created by the National Institute of Biomedical Innovation based on Pharmaprojects®/Informa, 2020.

Summary

As we have seen, the development of new drugs by Chinese pharmaceutical companies is becoming more active, especially in the past few years, and the number of products is rapidly increasing. The 13th Five-Year National Economic and Social Development Plan (2016-2020), which involves science and technology innovation policies, and China Manufacturing 2025, which describes future plans for the development of the manufacturing industry, both highlight biopharmaceutical development and manufacturing as one of the nation's key strategies, and the recent increase in the number of products developed and manufactured, as shown in Figure 1, is a reflection of these policies. The recent increase in the number of products developed and manufactured in China, as shown in Figure 1, can be attributed in part to the impact of these policies.

The majority of the products are anti-tumor drugs, and the development of biopharmaceuticals such as CAR-T cell therapy has been particularly active. Some of the products were designated as special measures by the FDA and EMA and have the potential for global development, especially by startup companies.

CAR-T cell therapy, for which R&D for commercialization is particularly active in China, has seen a succession of startups established and entered the market, mainly in Shanghai and Beijing, suggesting that the country is a fertile ground for the formation of bioclusters. On the other hand, many of the target antigens have already been reported, and there are issues in terms of novelty.

As shown in Figure 2, most of the new drug development by Chinese pharmaceutical companies is conducted only within their own country, and there are not yet many products that can be developed globally, which may be due to the novelty of each product. Although each item needs to be examined closely, there is no doubt that new drug development is gaining momentum, and it is necessary to continue to monitor these trends closely.

( Tomoyuki Shibuguchi, Senior Researcher, Pharmaceutical and Industrial Policy Research Institute)

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