The Pharmaceutical Industry at a Glance Nationalities of companies that created NME products approved in Japan, the U.S., and Europe Focusing on Approved Products from 2010 to 2019

Printable PDF

Tomoyuki Shibuguchi, Senior Researcher, Pharmaceutical Industry Policy Institute

Introduction

The Pharmaceuticals and Industrial Policy Research Institute (PIIPRI) has been investigating the basic ^patents1) for each of the top 100 pharmaceutical products in terms of global sales, and has continuously surveyed and reported on the companies that created the pharmaceutical products at the time of ^filing2). We have also conducted surveys focusing on orphan drugs and items that have received special regulatory treatment in Japan, the U.S., and ^Europe3). In addition to the previous analysis, we conducted a nationality survey of companies that created drugs approved as New Molecular Entity (NME) in Japan, the U.S., and Europe during the 10-year period from 2010 to 2019 in order to understand more recent NME results and the overall trend of NME creation.

Research Methods

NMEs were those identified as NMEs by each review organization based on the approval information and analysis results of each organization used in "Comparison of New Drug Approval Status and Review Periods in Japan, US, and Europe " ⁴⁾ as reported by Yoshida et al. in Policy Research Institute News No. 61.

The basic patents of each item were identified based on the patents classified as "Product" among the patents recorded in "Patent" of each item using Cortellis Competitive Intelligence of Clarivate Analytics, Inc. The nationality of the company or institution that created the patents has not been included in the previous research. As in previous surveys, the nationality of the applicant/assignee of the patent was used as the nationality of the company/organization that created the patent, but if there was an overseas parent company at the time of application, the nationality of the parent company was used. Note that some products could not be identified due to the absence of patents or other reasons.

Nationality of companies creating NMEs approved in each of the poles of Japan, the U.S., and Europe

The top 10 countries in terms of the nationality of the company that created the NME approved during the 10-year period from 2010 to 2019 (7 years from 2013 to 2019 in Europe) are summarized in Figure 1.

In Japan, 398 products were approved as NMEs during this period, with a total of 19 countries creating NMEs. The United States had the largest number of NMEs (165.5), followed by Japan (62), Switzerland (29), the United Kingdom (29), and Germany (29). Despite the differences in percentage and ranking, the trends were basically the same as those reported in previous editions of Policy Research Institute News.

The number of items approved as NMEs in the U.S. was 378. Japan was second with 40.5 NMEs, followed by Switzerland (31.5), Germany (27), and the United Kingdom (22).

For Europe, the data is for the period 2013-2019 due to data availability. There were 257 products approved as NMEs during this period, with 19 countries of origin. In Europe, the United States had the largest number of NMEs, accounting for more than half (139), with Japan coming in second with 28. Switzerland (21.5 items), the United Kingdom (18 items), and Germany (15 items) followed.

In all countries/regions, Japan was in second place. The United States, Japan, and European countries, including Switzerland, the United Kingdom, and Germany, were the major source countries, but there were also several items from South Korea and China.

NMEs approved in two or more poles of Japan, the U.S., and Europe (first approved items since 2010)

The results in the previous section include local drugs developed only in each country or region. For the purpose of examining the nationality of the company that created the globally deployed drugs, the items shown in Figure 1 were selected from those approved in two or more regions (i.e., Japan, the U.S., and Europe) ⁵⁾. In addition, we checked the approval status of each product before 2010 or in 2020, and selected products that were approved for the first time in 2010 or later in two or more regions. As a result, 308 items met this criterion, of which 171 items, the largest number, were approved in all three regions (Figure 2). Of the 110 items approved only in the U.S. and Europe, 43 are under development in ^Japan6) and may be approved in the future. In the following sections, 308 items were analyzed.

Characteristics of globally approved NMEs

Figure 3 summarizes the efficacy ^categories7) and ^{modalities8) of the} 308 items selected in the previous section. In terms of efficacy category, anti-tumor agents accounted for the largest number of 76, followed by general systemic anti-infective agents (47), gastrointestinal and metabolic agents (34), blood and body fluid agents (30), and immunomodulators (30). In terms of modalities, small molecules accounted for 179 products, or nearly 60% of the total. This was followed by monoclonal antibodies including ADCs (56 items) and recombinant proteins (37 items). Also included were nucleic acids, CAR-T, gene therapy, and other modalities that have been garnering attention in recent years.

Nationality of the company that created the globally approved NME

The 308 globally approved products were classified according to the nationality of the company that developed the product. There were a total of 17 countries that produced the products, and the results for the top 10 countries are summarized (Fig. 4 left). Japan ranked second only to the U.S., with 35 products in this category. The same information as in Fig. 1 was found for the top 10 countries and regions, with the exception of three products from South Korea. As reported by Kagii in Policy Research Institute News No. 61, ⁹⁾ Korean companies have been developing new drugs, and future trends will be watched closely. Figure 4 (right) shows the annual trend of 308 drugs based on the year of first approval, which is a cumulative total of 3 to 4 years since 2010. While the annual trends show a U.S.-dominated trend, Japan was second or third in the number of NMEs in each period, indicating that Japan has been continuously creating NME seeds as a leader in the creation of globally used drugs.

Nationality of the company that created the modality

Figure 5 summarizes the nationalities of the companies that created the three most popular modalities shown in Figure 3. There were 179 small molecule items, 16 of the 17 countries included in Figure 4. Japan ranked second after the U.S. with 30 products, followed by Switzerland (15.5 products), the U.K. (14 products), and Germany (10 products), showing the same overall trend as the ranking in Figure 4.

There were 56 monoclonal antibodies including ADCs, and the number of countries of origin was 7. Following the United States (31 products) and Switzerland (9 products), Japan ranked third with 5 products, the same as the United Kingdom. Japan was found to have created monoclonal antibodies, one of the biopharmaceuticals, although the rank and percentage is lower than that of small molecules.

Recombinant proteins (37 items), the third most common modality, was created by seven countries. The U.S. ranked first, accounting for more than 60% of the total with 24 items, followed by Denmark (5 items) and Canada (3 items). The ranking and country of origin differed from the aforementioned small molecule and monoclonal antibody categories.

Three products were approved globally in South Korea, two of which were small molecules and one of which was a recombinant protein.

Modality and Drug Classification

In the previous section, we saw that the countries where recombinant proteins were produced tended to differ from those of small molecules and monoclonal antibodies. In order to investigate the background of this trend, we investigated each modality and its medicinal classification.

As shown in the left side of Fig. 6, small molecules covered almost all of the drug classes shown in Fig. 3 (13/14 drug classes), and the product percentages were the same as those of the other drug classes. The monoclonal antibodies including ADCs were mainly used as anti-tumor agents and immunomodulators. Among recombinant proteins, gastrointestinal and metabolic drugs and blood and body fluid drugs accounted for more than 70% of the total. Although not shown in the figure, the results were concentrated in some of the above two medicinal use categories. Specifically, in the former category, the drugs were diabetes drugs such as insulin preparations, and other gastrointestinal drugs and metabolic drugs, which are often found in orphan drugs. In the latter category, most of the drugs were classified as anti-hemorrhagic drugs. Recombinant proteins are used in a somewhat limited range of therapeutic areas, reflecting the technology and the nationality of the companies that specialize in these areas of therapeutic use.

Annual change in modality

Next, we examined the annual trends of the three modalities by year of first approval (Fig. 7). Small molecules had the largest number of items in each period (Fig. 7 left). On the other hand, in terms of the percentage of total items, there was a gradual downward trend, with about 65% in 2010-2012, but this percentage dropped to about 50% in 2016-2019. On the other hand, the number of approved monoclonal antibodies has been increasing in both number and percentage, accounting for less than 30% of the total in 2016-2019. No major changes were observed for recombinant proteins.

Country of origin and modality

Finally, the relationship between the country of origin and the modality was investigated. As shown in Fig. 8, the U.S. has a large number of products, including high-profile modalities such as nucleic acids and CAR-T, and the trend is the same as the ratio of each modality in the globally approved products. On the other hand, Japan had 30 out of 35 products, with small molecules accounting for more than 80%, and the rest were monoclonal antibodies including ADCs (5 products). In Switzerland, the U.K., and Germany, where the number of products is similar to that of Japan, small molecules and antibodies accounted for most of the products, but there were products in several other modalities. During the survey period, Japan produced only small molecules and monoclonal antibodies, but before that, other modalities such as peptides were also produced. There were several items approved only in Japan for recombinant proteins and vaccines, but not in terms of items approved in more than one region.

Summary

As we have seen, Japan was the second largest creator of products approved as NMEs from 2010 to 2019, both in terms of countries/regions and in terms of products approved in two or more regions. Although the share of U.S.-origin products accounted for more than half of the total, and there is a tendency for the U.S. share to increase with each passing year, the results indicate that Japan is in a certain position in the world as a leader in the creation of medicines for global use.

In addition, the characteristics of the companies that created the drugs and their drug classifications were investigated with a focus on the modality. Although Japan's tendency to specialize in small molecules was recognized once again, it was found that Japan is also contributing to the creation of biopharmaceuticals, particularly monoclonal antibodies. In addition, although not included in the survey period, Biltrasen (product name: Biltepso®), a nucleic acid medicine discovered by Nippon Shinyaku for the treatment of Duchenne muscular dystrophy, was approved in Japan and the United States in 2020, and we expect to see more modality diversification of Japanese discoveries in the future.

Modalities should be selected based on what is best suited for the treatment of the target disease, and a new modality is not necessarily the best. In addition, there may be some mechanisms that can be substituted by small molecules, and having strengths in small molecules is considered an asset. At the same time, it is certain that there are disease mechanisms and therapeutic measures that can be elucidated for the first time through new modalities, and it is necessary to build the capacity to actively utilize them as a means of drug discovery in order to continue creating new drugs in the future.

Return to News List

TOP