DDW Multimedia Editor Megan Thomas takes a broad look at the drug discovery and development landscape in Japan and highlights how it is bolstered by government policies, investment, collaboration, start-up ecosystems and academic research.
Japan continues to be one of the largest pharmaceutical markets in the world, despite what the International Trade Administration described as ‘a challenging business landscape due to demographics’1. Moreover, the administration says that the Government of Japan’s efforts to ‘contain healthcare expenditure will continue to create a challenging pricing environment; however, the market is expected to remain the third largest and one of the most important destinations for US and foreign biopharmaceutical companies due to continued demands for innovative therapies’1.
Overview
According to the International Trade Administration’s market overview, anti-tumour agents brought in the largest sales in 2020 in Japan. These agents have remained the top selling pharmaceuticals in the therapeutic category in recent years and, due to Japan’s aging society, continue on an upward trajectory1.
The report stated: “Other top-selling pharmaceuticals that exhibited growth by therapeutic category included diabetes agents, antithrombotic agents, and ophthalmic agents. By pharmaceutical type, biopharmaceuticals are expected to grow even though the overall pharmaceutical market growth is projected to be negative. Many of the top-selling pharmaceuticals are biopharmaceuticals; however, the products account for approximately 15% of overall sales in Japan, which is significantly lower than the global biopharmaceutical sales ratio of approximately 30%. Similarly, biosimilars are expected to grow. While the number of antibody drugs sold in Japan is on the rise, approximately 90% of the products are manufactured overseas, indicating a high degree of dependence on overseas manufacturing bases.”
Government policies
There are a range of reasons why we should look on the Japanese market with interest and optimism, one of which is the Japanese government policies to improve the business environment. There are efforts across the country to promote digitisation after its importance became apparent during the Covid-19 pandemic and this is visible in both the public and the private sector.2
In June 2022, a basic policy was established for a “Digital Garden City Nation”, an initiative which aims to achieve “rural-urban digital integration and transformation”2. The vision has four priorities:
- Implementing digital services to solve rural issues
- Building a nationwide digital infrastructure
- Developing and securing human resources with digital skills
- Creating initiatives to leave no one behind
The initiative is expected to have impacts across all industries and innovations fields, from FinTech to HealthTech, InsurTech to RegTech. This is unsurprising – our drug discovery industry does, after all, centre itself around creating initiatives that leave no one behind, from cancer therapies to malaria vaccines.
Investment and collaboration
Both the manufacturing and the healthcare industries in Japan are undergoing positive transformation. According to the Japan External Trade Organization (JETRO), Japan’s upper hand on ageing populations, advanced technologies and solutions means they are continuously developing in the fields of medical devices, regenerative medicine, pharmaceuticals, and preventive medicine. Considering that Japan has the highest numbers of elderly people, the country has become ripe for investment in the healthcare industry.3
JETRO says: “Areas such as R&D in advanced semiconductors are being prioritised, and that’s in addition to sectors—such as automobiles and robotics—where Japan has traditionally been strong. Here, too, foreign entities are investing in—and collaborating with—Japanese companies.”3
Start-up ecosystem
As a country with an internationally recognised status of having the world’s third-largest economy, which is bolstered by the international corporations, SMEs, modern infrastructure and advanced technology, it can be easy to overlook the start-up ecosystems that form the bedrock of this status.
JETRO says: “Start-up ecosystems are ideal platforms for bringing together innovators to develop new technologies and solutions, as well as to establish next-generation companies across the country. Such hubs can become the springboard for launching new opportunities for cross-border, collaborative partnerships between Japanese and international entities—in areas like open innovation, where companies open their innovation strategies to entities outside their own portfolio of companies.
“Japan is evolving with such ecosystems. Kawasaki King Skyfront, for example, is located in Kawasaki, a city in Kanagawa Prefecture, which lies near Tokyo. Kawasaki King Skyfront is an R&D center with a focus on life science and environmental fields—and the realisation of open innovation projects. Osaka Innovation Hub (OIH), meanwhile, is an ecosystem backed by Osaka City, the capital of Osaka Prefecture. OIH hosts international start-ups, media and investors, in addition to running incubation and acceleration programs for ventures in a wide range of industries—from healthcare to life science to manufacturing.”3
Academia and research
With regards to academic research, a vat of Japan’s strength lies in its universities, R&D centres and academic institutes. Across this field, there are efforts to facilitate innovation, whether that’s through university spin-offs by researchers, or through open innovation collaboration between researchers, corporations and start-ups.
For example, CELLINK, a bioconvergence start-up that designs and supplies technologies and services to enhance biology research, opened operations in Japan and established a representative office at the Kyoto University Venture Incubation Center (KUViC). CELLINK Corporation, the Japanese subsidiary, was established in 2020 in Kansai, a region renowned for life sciences research facilities and corporations3.
JETRO says: “Tohoku University, meanwhile, has established the Clinical Research, Innovation and Education Center (CRIETO)—a life science hub with a goal of bringing ideas created in the lab to the market. Hosted by Tohoku University Hospital, CRIETO engages in international collaborations with leading universities, research institutes and companies—including foreign-affiliated ones—as part of its innovation strategy.
“In 2018, for instance, Tohoku University signed a partnership agreement with Phillips Japan, a subsidiary of Dutch multinational Phillips, to conduct joint research in the field of healthcare. Two years later, in 2021, the university and the Dutch firm extended the collaboration, entering a seven-year strategic research contract to explore remote training of anesthesiologists and to deploy artificial intelligence to analyse chronic heart disease. Indeed, Phillips has a co-creation space at Tohoku University’s CRIETO hub.
Not to mention, The University of Tsukuba has established an initiative called the Tsukuba International Center for Digital Biotechnology3. As well as other projects, the centre promotes international cooperation and the creation of advanced solutions in collaborative medicine and food products. JETRO says: “Supported by the Japan Science and Technology Agency, the centre seeks to tackle challenges identified in the sustainable development goals (SDGs) of the United Nations, and in Japan’s national strategy for innovation, including a goal to provide health and wellbeing for all and to create the foundations for industrial and technological innovation.”
Regulatory
PMDA (Pharmaceuticals and Medical Devices Agency) is the Japanese regulatory agency, which works alongside the Ministry of Health, Labour and Welfare to deliver safe and effective drugs to not just Japan but the international market.
Since 2017, Japan’s PMDA has had the Conditional Early Approval System, which speeds up the practical application of drugs that target serious, debilitating diseases4. This was initially for the conditional approval pathway for medical devices (July 2017), but since October 2017 this has included pharmaceuticals. The approval system allows early applications to be admitted without confirmatory clinical trials, on the condition that the product’s safety and efficacy be further evaluated while on the market. What is more noteworthy is that products eligible for Conditional Early Approval are not restricted to orphan drugs.
To this end, pharmaceutical company ViiV Healthcare received approval in Japan for its long-acting HIV treatment in May 20225. As reported by DDW, Deborah Waterhouse, CEO of ViiV Healthcare, said: “At ViiV Healthcare, we are committed to leading innovation in HIV treatment to offer solutions to match the needs of people living with HIV. By removing the need for daily oral treatment, the approval of cabotegravir injection and rilpivirine long-acting is an important development for the HIV community and reinforces our efforts to provide new treatment options so that no person living with HIV is left behind. We look forward to working closely with partners over the next few years to make this treatment available to people who could benefit from long-acting treatment in Japan.”
Real-world evidence
It is clear that the foundations for drug discovery and development in Japan are strong, but how does that reflect in what is happening currently in the real world?
Recently, Daiichi Sankyo, the second-largest pharmaceutical company in Japan, initiated Phase III trials of its Covid-19 vaccine, DS-5670, in healthy unvaccinated adults6. The company will continue consultation with regulatory authorities to deliver a domestically produced mRNA vaccine to Japanese people as soon as possible.
In August 2022, scientists from Tokyo University of Science published a new study which reveals that the yeast Eps15-like endocytic protein Pan1p is a key player in endocytosis7. As reported by DDW, the team of scientists from Austria and Japan, led by Prof Jiro Toshima (Tokyo University of Science) and Prof Junko Y Toshima (Tokyo University of Technology) conducted a set of experiments where the location of Pan1p was altered to peroxisomes from the cell membrane.
Meanwhile, a new Alzheimer’s disease (AD) treatment has been shown to reduce clinical decline in mild cognitive impairment due to AD and mild AD with confirmed presence of amyloid pathology in the brain. Eisai and Biogen’s anti-amyloid beta (Aβ) protofibril antibody lecanemab met the primary endpoint and all key secondary endpoints in the global Phase III Clarity AD clinical trial and Eisai has stated its intention to file for regulatory approval in the US, Europe and Japan by March 2023.
The future looks bright and consistent for the life sciences and specifically for drug discovery in Japan, especially in the post-pandemic landscape which relies on technology, opportunity, research infrastructure and government support. The drug discovery community should be seriously considering the Japanese landscape when thinking about everything from early-stage clinical trials to drug development and the business landscape in between.
References
- https://www.trade.gov/country-commercial-guides/japan-pharmaceuticals#:~:text=According%20to%20the%20Ministry%20of,from%202019%20in%20yen%20terms).
- https://www.jetro.go.jp/en/invest/insights/japan-insight/reasons-invest-launch-business-technology-japan.html
- https://www.jetro.go.jp/en/invest/insights/japan-insight/future-investment-collaboration-major-industries.html
- https://globalforum.diaglobal.org/issue/may-2018/pmda-puts-regulatory-approval-on-a-fast-track/
- https://viivhealthcare.com/hiv-news-and-media/news/press-releases/2022/may/viiv-healthcare-announces-marketing-approval-by-japan/#:~:text=YouTube-,ViiV%20HEALTHCARE%20ANNOUNCES%20MARKETING%20APPROVAL%20BY%20JAPAN’S%20MINISTRY%20OF%20HEALTH,LONG%2DACTING%20TREATMENT%20FOR%20HIV
- https://www.daiichisankyo.com/files/news/pressrelease/pdf/202209/20220901_E.pdf
- https://www.tus.ac.jp/en/mediarelations/archive/20220824_5729.html
