The Pharmaceutical Industry at a Glance Nationality of companies generating top pharmaceutical sales in the Japanese market

Akira Nakao, Senior Researcher, Pharmaceutical and Industrial Policy Research Institute

Introduction

The National Institute of Biomedical Innovation Policy (NIBIO) has surveyed and reported on the nationalities of the companies that created the top 100 pharmaceuticals in the world at the time of invention by examining the basic ^{patents1) of} each product ^.2) In the November 2021 issue of NIBIO News No. 64, Japan was ranked third in the world for drug creation after the United States and Switzerland, and was the only country in the world where drug discovery is possible. ^{3), 4).}

In this study, the author surveyed the nationality of companies that create drugs marketed in Japan as a basis for examining whether Japan's drug discovery capabilities are being returned to the people living in Japan and contributing to their access to new drugs.

Survey Method

Based on data from IQVIA's World Review Analyst 2021, Top 70 Product Sales Trends for the top 70 products in the domestic pharmaceutical market in Japan and four other countries (the United States, Switzerland, the United Kingdom, and Germany), the basic ^patents1) for each product in 2020 were investigated to The country of origin was determined. The nationality of the originating company to which the rights to the pharmaceutical product are attributed is the nationality of the applicant/assignee company listed in the above patents, but in the case of companies with multinational operations, the nationality of the parent company is used. Therefore, if there is a parent company at the time of application, the nationality of the parent company does not necessarily coincide with the nationality of the applicant's company. This is because we considered the contribution of the parent company in terms of resources such as human and financial resources in the process of inventing key substances, applications, technologies, and other elements.

Number of drugs by nationality of companies creating the top products in terms of sales in the Japanese market in 2020

According to IQVIA World Review Analyst 2021, pharmaceutical sales in the Japanese market in 2020 were $88.6 billion. The top 70 drugs in this category accounted for $25.6 billion in sales, or approximately 29% of the ^market5).

The number of drugs by nationality of the company generating the top 70 drugs in Japan (Figure 1) and the number of drugs by nationality of the company generating the top 100 drugs in the world (Figure 2) are shown below for comparison.

The United States has the largest share of 29 products (43%) in the top 100 products in Japan, followed by Japan with 16 products (24%), Germany with 7 products (10%), Switzerland with 6 products (9%), the United Kingdom with 5 products (7%), Sweden with 2 products (3%), and Belgium, Denmark, and Norway with 1 product each. Norway had one product in each category. The share of Japanese-origin medicines among the top-selling products in the Japanese market was higher than the share of Japanese-origin products among the top-selling products in the global market ( ^9%3 ). The survey also included a survey on the characteristics of 16 Japanese products, the overseas approval status of these products, and whether or not they are ranked among the top 100 drugs in terms of global sales, as well as an analysis of the technical classification of active ingredients and the classification of medicinal effects. The difference between the number of products of Japanese origin in the top products in global sales and the number of products of Japanese origin in the top products in sales in the Japanese market was analyzed.

Fig. 1 Number of drugs by nationality of the company creating the drug in the top products in terms of sales of drugs in the Japanese market

Figure 2 Number of Pharmaceuticals in the Top 100 Global Pharmaceuticals Sales by Nationality of the Company Creating the Drug

Overview of Products of Japanese Origin in Top Sales in the Japanese Market in 2020

Of the 16 Japanese-origin products that accounted for the top-selling products in the Japanese market, 9 were global products that were approved and launched by at least one of the European or US review ^{organizations6)} other than Japan, while the other 7 were non-global products sold mainly in ^Japan7).

Of the nine global products, four were ranked in the top 100 products in terms of global sales in 2020, and one had been ranked in the past. The remaining four products had been ranked in the top 300 by IQVIA World Review Analysts within the last three ^years8).

On the other hand, three of the nine products of Japanese origin ranked in the top 100 products in terms of global sales in 2020, but not among the top five products in the Japanese market, are drugs for diseases for which there are fewer patients in Japan than in the rest of the world, one has been on the market in Japan for a short time, and one was ranked in the top 70 products in terms of Japanese market pharmaceutical sales in 2019. ⁸⁾.

Figure 3: Top 100 Global Pharmaceuticals by Sales in Japan and the World

Figure 4: Technology Classification of the Top Global Sales of Pharmaceuticals in the Japanese Market

As for the seven non-global products, there were three brand-name drugs (so-called long-listed drugs) for which generics existed as of December 31, 2020, and the majority, four, were brand-name drugs without ^generics9) (Figure 3).

Number of products of Japanese origin in the top products in terms of sales in the Japanese market by technology and drug category

The technical classification of the active ingredients in the top-selling drugs in the Japanese market (synthetic chemically synthesized drugs and biopharmaceuticals) was 43 (63%) for synthetic chemically synthesized drugs and 25 (37%) for biopharmaceuticals. The ratio of synthetic chemical drugs to biopharmaceuticals in the top 100 products in terms of global sales was 55: ⁴⁵³⁾, indicating that synthetic chemical drugs were more dominant in the top products in the Japanese market. 3) On the other hand, in the technology classification of products originating in Japan, synthetic chemical drugs accounted for 13 products and biopharmaceuticals for 3 products, with synthetic chemical drugs accounting for 81% (Figure 4).

In order to examine the characteristics of each disease in the global and Japanese markets, a comparison was made in terms of the percentage of each drug's efficacy classification (ATC code Level 1). In the Japanese market, 26 (38%) of the top-selling drugs were classified as antineoplastics/immunomodulators (L), followed by gastrointestinal and metabolic (A), skeletal muscle (M), and central nervous system (CNS) drugs with 9 (13%), 8 (12%), and 6 (9%) sales, respectively.

The top 100 drugs in terms of global sales were classified into L (32%), A (19%), J (general systemic anti-infectives) (13%), and N (12%), in that order. ³⁾ The L, A, and N categories were commonly found among the top products in Japan and the rest of the world. The L, A, and N classifications were the most common diseases in both the global and Japanese markets.

On the other hand, in the Japanese market, the percentage of J-classified products was low (3%, 2 products), while that of M-classified products (12%, 8 products) and C-classified products (drugs for circulatory organs) (6%, 4 products) was high compared to the rest of the world. Of these, the percentage of M-classified drugs in Japan was 12%, compared to 3% in the rest of the world, suggesting that M-classified drugs are unique to Japan. Another feature of this category was the inclusion of 4% (3 products) of H-classified systemic hormones (excluding sex hormones), which were not included in any of the top 100 products in terms of global sales (Fig. 5).

Next, looking at the number of products of Japanese origin in the top 100 products in terms of sales in the Japanese market by ATC drug classification and their share, the number of products of Class A and Class M was high (both 4 products), and their share was as follows: Class G (1/1, 100%), Class M (4/8, 50%), Class C (2/4, 50%), Class A (4/9, 44%), and H (1/3, 33%), which accounted for much more than the 24% share of Japanese-origin items overall. Although 3 items were included in Classification L, which accounted for the highest percentage of the top-selling items in the Japanese market, the percentage was relatively low at 12% (3/26) (Fig. 6).

Fig. 5 Classification of top selling drugs in the Japanese market and the world

Figure 6: Classification of Japanese-origin products in the top 100 drugs by sales in the Japanese market

Analysis of drug classes that are unique to the Japanese market and have a high proportion of products of Japanese origin

In terms of the proportion of efficacy categories among the top-selling drugs in the global and Japanese markets, skeletal muscle drugs (ATC Category M) accounted for 12% (8/68 products) in Japan, compared to 3% in the global market. In addition, 50% (4 products) of the 8 M-classified products were of Japanese origin. Although there are other drug classes, such as C and H, that are unique to the top-selling products in the Japanese market and have a high percentage of products of Japanese origin compared to the rest of the world, we focused on M, which has the highest number and percentage of products in this category, and investigated the eight products in this category down to their indications in order to analyze the high number of M products in the Japanese market. The results of the survey were as follows.

As a result, the following three indications were found to be the main indications for the eight products, and it was considered that these three indications may be characteristic of the Japanese ^market10).

Rheumatoid arthritis
Analgesic and anti-inflammatory for pain such as rheumatoid arthritis, osteoarthritis and lumbago
Osteoporosis

With regard to rheumatoid arthritis drugs, some items with multiple indications were classified as L in their ATC classification, and with regard to osteoporosis, some items were included in ATC classifications other than M. Therefore, we re-examined how many items with the above three indications were included in the top-ranked items. As a result, there were 13 items out of 68 items with the above three indications, of which 5 items (38%) were drugs of Japanese origin and 4 out of 5 items were non-global ^products11). In other words, for these three diseases, products of Japanese origin accounted for a relatively high percentage of the total, and were mainly used in the Japanese market, not in the US or European markets.

Analysis of three disease backgrounds

When considering the characteristics of diseases in the domestic market, there is a limit to what can be determined from a single characteristic, as they are intricately related to not only environmental and genetic factors such as lifestyle, but also geographical factors, healthcare systems and policies, economic conditions, and various other factors in the country or region. However, the keywords "rheumatoid arthritis," "pain relief and anti-inflammation," and "osteoporosis," especially the latter two diseases, may bring to mind "aging" as one of the ^factors12). Figure 7 shows the percentage of the population aged 65 and over in representative OECD countries and some non-OECD countries, and Japan shows an overwhelmingly high "aging rate" (28.8%) compared not only to the world average (9.3%) and the G20 average (11.6%) but also to Western ^countries13).

Fig. 7 Percentage of population aged 65 and over in countries around the world

In addition, as noted in the report by ^Ito14), the Ministry of Health, Labour and Welfare's National Survey of Basic Living Conditions reported that the top four and five major causes of the need for nursing care are "fractures/falls" and "joint diseases," ^{respectively15)} (Fig. 8). The high percentage of these diseases as causes of long-term care and the fact that anti-inflammatory analgesics for pain related to osteoarthritis and osteoporosis are among the top-selling drugs in the Japanese market, given the aging of the Japanese population, suggest that the percentage of drugs for these diseases in the Japanese market is higher than that in overseas markets. In such a situation, the number of drugs related to these diseases is high. In this context, it was found that many of the drugs related to these diseases are of Japanese origin.

Fig. 8 Composition ratio of major causes of the need for long-term care

Differences in the proportion of products of Japanese origin among the top-selling drugs in the global and Japanese markets

In order to find out the reason for the difference between the number of products of Japanese origin in the top 100 products in global sales and the number of products of Japanese origin in the top 100 products in sales in the Japanese market, the top five countries with the largest number of products in the survey of nationalities of origin in the top 100 products in global sales were surveyed to determine the country of origin of each product based on data for the top 70 products in sales in the domestic market of each country. The top five countries with the highest number of products in the survey of the top 100 products in global sales were investigated.

Fig. 9 Percentage of nationalities of companies that created the top-selling products in the domestic market in Japan, the U.S., and Europe

As a result, in all of the four Western countries except Japan, the United States and Switzerland, in descending order, had a high percentage of drug discovery products in their domestic markets, with Japan, the United Kingdom, and Germany in the third group, which is the same trend as that observed in the nationality survey of the top 100 products in global sales. On the other hand, in the Japanese market, unlike other markets, Japan is in second place, with a large difference from the third place group, indicating that the proportion of drugs originating from Japan in the Japanese market is outstanding (Fig. 9).

Summary and Conclusion

As a basis for examining whether the drug discovery capabilities of Japan, one of the limited countries in the world capable of drug discovery, are being passed on to the people living in Japan and contributing to their access to new drugs, we examined the nationality of companies that create drugs sold in Japan.

Products of Japanese origin accounted for a certain number of the top-selling products in the Japanese pharmaceutical market, which was considerably higher than the share of products of Japanese origin in the top-selling products in the global pharmaceutical market. The majority of the top-selling products in the Japanese market were global products, and more than half of these products had been ranked in the top 100 products in terms of global sales. Some of the top-selling products in the Japanese market were of Japanese origin, and many of them were non-global products. These facts suggest that Japanese pharmaceutical companies may have contributed to the Japanese public's access to new drugs by developing new drugs for the global market as well as conducting research and development of new drugs tailored to disease characteristics in Japan.

On the other hand, while the percentage of anti-cancer and immunosuppressant disease areas is high among the top-selling products in the Japanese market, and biopharmaceuticals account for just under 40% of total sales, Japan has not fully demonstrated its presence in these disease areas and technology categories. In order for Japan to continue to be one of the world's leading drug discovery countries and to deliver innovative new drugs to people not only in Japan but also around the world, it will be necessary to maintain and strengthen its drug discovery capabilities by expanding the frontiers of chemical synthesis technology, which is one of its strengths, while reinforcing efforts in areas and fields where there is a shortage.

1) Number of reports and countries from which data was obtained

Basic patents in this study refer to patents that are key to each item, such as substance patents and use patents.
2)

Pharmaceutical and Industrial Policy Research Institute, "Drug Creation and Rights Attribution from the Perspective of Nationality of Country and Company," Policy Research Institute News No. 42 (July 2014); thereafter, Policy Research Institute News No. 47 (March 2016), No. 50 (March 2017), No. 52 (November 2017), No. 55 (November 2018), No. 58 (November 2019), No. 61 (November 2020), and No. 64 (November 2021), reported in.
3)

Pharmaceutical Industry Policy Institute, "Nationality of Companies Generating Top Global Sales of Pharmaceuticals: Trends in 2020," Policy Institute News No. 64 (November 2021). (Reference date: February 8, 2022)
4)

National Institute of Pharmaceutical and Industrial Policy, "Review of the Survey on Nationalities of Companies Generating Top Global Pharmaceutical Products in terms of Dynamic Trends in the Number of Products and Leaders in Drug Discovery," Policy Research Institute News No. 64 (November 2021). (Reference date: February 8, 2022)
5)

Converted into U.S. dollars using quarterly exchange rates (3-month average).1The currency rate from Japanese yen to U.S. dollars was 0.00918282 in 1Q; 0.00918282 in 2Q; 0.00918282 in 3Q; 0.00918282 in 4Q.CopyrightⒸ 2022 Prepared by the Pharmaceutical Industry Policy Institute based on IQVIA World Review Analyst, Data Period 2020 (All rights reserved).
6)

The U.S. Food and Drug Administration (FDA) or European Medicines Agency (EMA).
7)

The approval status in Japan, the U.S., and Europe was researched based on the public information of the Pharmaceuticals and Medical Devices Agency (PMDA), the FDA, and the EMA, and "Tomorrow's New Drugs" (Technomic, Inc.) Clarivate Cortellis Competitive Intelligence.
9)

Information on the NHI Drug Price Standard List and Generic Drugs (until March 31, 2021)" (Ministry of Health, Labour and Welfare) (Reference date: February 8, 2022)
10)

The indications were surveyed using each drug's package insert, "Tomorrow's New Drugs" (Technomic Co., Ltd.), and the KEGG DRUG Database https://www.genome.jp/kegg/drug/drug_ja.html. Some products contain multiple indications in one item. OECD Stat.
11)

When the indications were "analgesic and anti-inflammatory for pain" and "osteoporosis," 8 out of 68 drugs were listed, of which 4 (50%) were drugs originating in Japan. All four were non-global products.
12)

Rheumatoid arthritis includes both elderly-onset rheumatoid arthritis (EORA) and adult-onset rheumatoid arthritis (AORA), and it has been reported that the age of onset and patient age is also getting older as the population ages.
(a) Kato E, Sawada T, Tahara K, et al: The age at onset of rheumatoid arthritis is increasing in Japan: a nationwide database study. Int J Rheum Dis. 20: 839- 845,2017. (b) Kuwana, M.: "-Topic: Is rheumatoid arthritis no longer a disease of the elderly?" J Med Med J. 16(2): 117-118, 2020.(Reference date: February 8, 2022). (c) Susumu Nishiyama, Tetsushi Aida, Yasuhiko Yoshinaga, Shoji Miyawaki, Shigeto Toma: "Survey of Elderly Rheumatoid Arthritis Patients," Clinical Rheumatology, 31: 285-293, 2019. DOI (date of reference: February 8, 2022)
13)

OECD Stat. Historical Population, Data extracted on 20th Jan 2022.
14)

Pharmaceutical and Industrial Policy Research Institute, "Health Status of the Elderly from the Perspective of Nursing Care System Data: Analysis Using Complementary Indicators of Healthy Life Expectancy," Policy Research Institute News No. 65 (March 2022).
15)

2019 Basic Survey of National Life Expectancy," Ministry of Health, Labour and Welfare, Japan. (Reference date: February 8, 2022)

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