Top News The 7th Nikkei-FT Conference on Infectious Diseases" held as a Pharmaceutical Association of Japan lunch session. Recommendations to strengthen future infectious disease control through industry-academia-government collaboration

In Japan, an action plan for AMR measures up to 2020 was formulated in 2016, and efforts have been promoted. This year, it is time to evaluate and reconsider the past five years. One of the directions in the Action Plan that we should take with regard to infectious diseases is "research and development of diagnostic methods and therapeutic drugs," but unfortunately we have not made sufficient progress in this area. One of the reasons for this is the business principle. Compared to drugs in the fields of oncology, respiratory medicine, and dermatology, infectious disease drugs are not profitable even if they are discovered, making it difficult for companies to advance their business. At the same time, however, the problem of resistant bacteria is steadily progressing in clinical practice, to the extent that it has been called a silent pandemic. We are faced with this dilemma. How can we solve this problem?

In the U.S., the "10 x '20 initiative" was announced in 2010, which set the direction for the creation of 10 new antimicrobial agents by 2020, and the government has taken the lead in this initiative. Meanwhile, in Japan, the Science Council of Japan handed a proposal to the government at the G8 Summit in 2013. The proposal states, "The problem of resistant bacteria is a threat to humanity, and should be considered a crisis management issue and addressed. However, despite such efforts, progress has been slow.

The problems with antimicrobial agents from a business perspective, namely, the extremely high cost of drug discovery research and development and the fact that the business model does not generate profits even after the product is launched, make it important to create incentives through cooperation between industry, academia, and government to make the business function well in the future. It will be important to create incentives through cooperation between industry, academia, and government to make it work as a business. Incentives include push-type incentives at the R&D stage and pull-type incentives after the product is launched. In particular, it has recently been discussed that pull-type incentives should be successfully created to promote difficult drug discovery. This problem cannot be solved by science alone. People from science (academia), economics (industry), regulatory (government), and other fields are joining together to discuss how to promote the development of necessary drugs to treat resistant bacteria.

In Japan, push-type projects for the development of drugs for infectious diseases are being promoted by the Japan Agency for Medical Research and Development (AMED) through the Creation of Innovative Infrastructure for Clinical Research and Development (CiCLE) project, but pull-type incentives are unfortunately still not yet in sight. After various discussions at the Nikkei-FT Conference on Infectious Diseases, we are finally beginning to see a form for these incentives.

The AMR problem is of such a nature that it is a silent pandemic and if we do not move now, we will be in serious trouble. This is exactly the kind of problem that needs to be promoted through collaboration between industry, academia, and government from a crisis management perspective. And AMR is a global problem, and we must consider global data sharing as a One Health issue. And it is also important to note that the direction of drug discovery is changing with the evolution of diagnostic methods. Diagnosis of infectious diseases, which used to take two or three days, can now be done in 30 minutes to determine bacterial resistance. In part, this change has been driven by the response to COVID-19. With this type of technology, it makes sense to continue developing very strong antimicrobials, even if the therapeutic target is narrow. This is another important direction. Another important direction is that, although the main focus of drugs for infectious diseases has been on bactericidal activity against microorganisms, as we learned in COVID-19, there is a possibility that inhibiting the cytokine storm on the host side will lead to treatment. I believe that "Host-directed Molecular Targeted Therapy" is the direction of future development.

The focus is now on drugs for infectious diseases, especially COVID-19, but what must we do as a country to ensure the rapid supply of such drugs? First of all, we must promote research and development, and then quickly conduct the approval review of the developed drugs, and secure the drugs that have been approved. At present, there are two drugs approved in Japan for the treatment of COVID-19, and the government has moved to secure these drugs and has set up a distribution system for them. Similarly, for vaccines, we are working to secure the vaccine through research and development, establishment of a production system, and negotiations with pharmaceutical companies. The COVAX Facility, an international framework, is mainly for developing countries, but Japan will also use this framework to secure vaccines.

Prime Minister Yoshihide Suga has declared that Japan will secure enough vaccines to provide to all citizens by the first half of 2021. To this end, supply contracts with vaccine development companies are being progressively signed, and a bill to establish a system to promptly promote vaccination will be submitted to the extraordinary Diet session.

To date, the government has invested a large budget for research and development to respond to COVID-19, securing 148.1 billion yen in total for FY2020. The money will be used, for one, to develop treatments and vaccines, as well as antigens and antibodies for PCR testing and diagnosis. The budget is also used for medical devices such as extracorporeal membrane artificial lungs (ECMO). In addition, for the development of basic technologies, support is provided for projects such as the analysis of the genome of COVID-19 patient specimens under the title of "Creation of Innovative Infrastructure for Development of Medical Research". In addition, to improve the environment, we are providing financial support for the development of a testing system at the National Institute of Infectious Diseases, the establishment of a network for clinical research trials in Asia to strengthen international collaboration, and international frameworks such as the Coalition for Pandemic Preparedness Innovation (CEPI) and the Gavi Vaccine Alliance.

Until now, vaccines have typically been inactivated vaccines, but with COVID-19, new technologies such as messenger RNA and viral vectors are emerging. I believe that European and U.S. pharmaceutical companies are taking the lead in vaccine development using such technologies. At the same time, it is necessary to develop a domestic production system, and the government is providing support for this.

I would like to talk about our efforts to secure vaccines as quickly as possible. Normally, the approval of a therapeutic drug or vaccine is a "research and development - regulatory approval - production" process. However, that would take years, so with regard to the COVID-19 response, we are looking to shorten this period considerably by moving forward simultaneously with the process of obtaining approval and the process of setting up a production line. To support this, we have secured a supplemental budget and are providing support to expedite the process. We have secured 10 billion yen in the first supplementary budget and 50 billion yen in the second budget for vaccine research. In addition, in order to simultaneously improve the production system, we are spending 137.7 billion yen, which we call the Emergency Vaccine Development Project. Furthermore, the budget is being used for negotiations with overseas manufacturers who are currently ahead of us in vaccine development and for the purchase of syringes and syringes.

In particular, under the name of the Emergency Vaccine Production System Improvement Project, support is being provided to manufacturers that meet certain conditions through public solicitation for the establishment of production lines in Japan.

At present, we have signed basic agreements with two overseas pharmaceutical companies to secure vaccines. We do not know how many vaccinations will be required, but we have agreed that each company will supply enough vaccine for 60 million people, or 120 million doses, in the first half of 2021. In addition, just recently we signed an agreement with another manufacturer to supply 50 million doses by the first half of the next fiscal year.

In order to ensure a prompt supply of needed treatments and vaccines, it is important to have a strong cooperative relationship between the public, private sector, and academia. The three parties must communicate and share information on a daily basis. I believe it is important to prepare for future pandemics by repeating such efforts.

Today, I would like to talk about the importance of international cooperation against novel coronavirus infections from both economic and Sustainable Development Goals (SDGs) perspectives.

At the Bill & Melinda Gates Foundation, we publish our progress on the SDGs every year, and for the year 2020, the statistics are all very sad for all of us at the Foundation. After two decades of steadily declining global poverty, this year, for the first time, it has begun to increase. The impression is that we have suddenly regressed to the poverty level of 10 years ago. In particular, looking at the situation of poverty among infants and toddlers under the age of 5, the results show that after halving over the past 30 years, it is expected to increase starting in 2020. There are also signs of an increase in stunted growth due to malnutrition. There are also very negative observations for other infectious diseases such as HIV and malaria, which are not new coronavirus infections. In terms of vaccine coverage, the first 25 weeks of 2020 show a 25-year regression. The results are disappointing not only for novel coronavirus infections, but also for various other areas of health care.

Amidst such a situation, the economic situation is said to be affected by the global economy shrinking by approximately 90%, with double the economic losses of the 2008 Lehman Brothers collapse. On the other hand, some predict that the economic loss will be 1,200 trillion yen despite the 1,800 trillion yen of economic stimulus measures that each country is now taking.

For the Gates Foundation, vaccines have been the main focus of our efforts, both for the SDGs and for economic recovery. Currently, developed countries with funds are the first to secure vaccines, and statistics show that approximately 138 trillion yen has been spent to secure these vaccines. An analysis shows that if negotiations had been conducted in accordance with international cooperation, including developing countries, the price could have been reduced to 1/13th of what it is today. In addition, while developed countries are able to secure 2.5 times as many vaccines per capita, developing countries are only able to secure about 14% of the vaccines for their population, creating a large disparity. According to other data, the number of deaths would be roughly twice as high if only developed countries supplied 2 billion doses of vaccine as if the entire world were supplied. These data clearly show the importance of international cooperation. The results of these analyses have reaffirmed the importance of building mechanisms and systems in accordance with international cooperation to deal with this new coronavirus infection and with AMR that may occur in the future.

In this environment, there is the Access to COVID-19 Tools (ACT) Accelerator, the world's only internationally coordinated mechanism for new coronavirus infection. Japan has participated in this mechanism since its inception. This mechanism is designed to ensure a fair and equitable supply of vaccines, therapeutic drugs, and test kits, including to developing countries. The goal is to supply 2 billion doses of vaccines to the world by the end of 2021, 245 million doses of therapeutics by the middle of 2021, and 500 million tests for test kits in low- and middle-income countries by the middle of 2021. The COVAX Facility for vaccines, among others, is a system under which developed countries, including Japan, can purchase vaccines from this facility, which is like the world's only buyer's club for vaccines covering the entire world.

So far, the Japanese government is said to have successfully implemented measures against novel coronavirus infection in Japan. On the other hand, Japan has so far demonstrated strong global leadership in the spirit of multilateralism. For example, Japan was the first developed country to announce its participation in the COVAX Facility. Since Japan was the first country to announce its participation in the COVAX Facility, more than 180 countries are currently participating in this facility. The COVAX Facility is a mechanism to secure vaccines for 20% of the Japanese population, and the Japanese government has decided to contribute US$130 million from its ODA budget to Gavi's Advance Market Commitment (AMC) for vaccines for developing countries. The government has decided to contribute $130 million from the ODA budget. In addition, the Japanese government has decided to contribute $98 million to CEPI, which is a push-type incentive for new coronavirus drugs. Thus, as an advanced country that recognizes the importance of multilateralism, Japan has been quick to participate in various initiatives and has created a trend toward international cooperation. I believe that the Japanese government has demonstrated strong leadership not only in domestic measures but also globally.

I would like to talk about the pharmaceutical industry's efforts and challenges in dealing with infectious diseases.

First, I would like to talk about the efforts of the pharmaceutical industry to develop a cure and vaccine for COVID-19. In order to shorten the development period of therapeutic drugs, companies are conducting tests on so-called repositioning to see if compounds that have already been approved can be used. In vaccines, companies are working to shorten the time it takes to provide products by conducting basic research and non-clinical and clinical trials in parallel, or by building and preparing production facilities from a stage when the success or failure of development is not yet known. In addition, in the development and production of vaccines, it is known that in the case of COVID-19, it cannot be produced using the chicken egg method, so companies are working on the use of new modalities such as messenger RNA and DNA and new production methods.

Despite these efforts to provide therapeutic agents and vaccines as quickly as possible, there are still no new therapeutic agents or vaccines that have been reliably verified to be effective. Even if the new coronavirus infection is contained, another infectious disease will surely appear in the future. In order to effectively promote countermeasures against infectious diseases, including research and development of medicines, we believe that a command post function is necessary to plan and promote national strategies from a time of peace.

In addition, it should be able to coordinate relevant ministries and agencies, clearly communicate policies to local governments and medical institutions, and promote technological innovations, human resource development, and the stable supply of pharmaceuticals through cooperation between industry, academia, and government. It is also necessary to promote technological innovation through industry-academia-government collaboration, human resource development, and the development of infrastructure for production facilities and stable supply of pharmaceutical products. Another important function of the command post is to promote international collaboration with the United States and other countries.

Among the functions that the command post should have, we, as an industry, propose measures that are necessary for the research and development of therapeutic drugs and vaccines, as well as for the stable supply of these products. For example, nucleic acids and viral vectors using genetic recombination technology are being utilized in the research and development of vaccines. These are innovative modalities that have never been used before. In order to promptly put such innovations to practical use, it is necessary to promote research and development through industry-academia-government collaboration even in normal times.

In addition to COVID-19, various other infectious diseases are threatening our lives around the world. AMR is a particularly important issue. The reason why AMR is an important issue is that, in addition to the large number of deaths, AMR, unlike other infectious diseases, is a crisis that can be predicted to some extent and prevented. The World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC) have already listed the organisms of concern, and we believe that prioritizing research and development of new drugs for these organisms will help prevent AMR from becoming a serious social problem.

The number of newly developed antimicrobial agents has been on a steady decline since its peak in the 1980s. Recently, two companies that had obtained approval for new antimicrobial agents went bankrupt. This is indicative of the harsh market environment for antimicrobial agents today, especially for AMR, and private companies are not making progress in AMR. On the other hand, the threat of AMR has been growing in recent years with the emergence of bacteria resistant to multiple antimicrobial agents; if antimicrobial agents against AMR run out, in addition to direct deaths from infection, necessary surgery may not be performed due to warnings of postoperative infection.

In order to solve the current problem, the AMR Action Fund was established in July of this year with the participation of more than 20 pharmaceutical companies from around the world. The fund plans to raise a total of $1 billion (approximately 100 billion yen) from pharmaceutical companies, making it the largest project ever undertaken by the pharmaceutical industry. The fund will not only provide funding for venture companies, but will also provide R&D companies with expertise and know-how in development and commercialization. The goal is to bring two to four new antibacterial drugs to market over the next 10 years.

However, we believe that the effectiveness of this fund will be limited: even if a therapeutic drug for AMR is successfully developed, the use of that new antimicrobial will be restricted as much as possible in order to avoid creating the next drug-resistant strain. In order for AMR R&D to continue, we believe it is necessary to create an environment in which private companies can continue to develop AMR therapeutics by introducing unprecedented policies such as pull-type incentives. Specifically, a manufacturing and marketing approval reward system, a regular fixed price purchasing system, and a sales guarantee system could be considered. We hope that these systems will be introduced on a trial basis starting in FY2022, and if there are no problems with their operation, we would like to see them become law.

The AMR Action Fund alone has limitations in solving problems, but if pull-type incentives are introduced, private companies, especially venture companies, will become more active and continue to produce new antimicrobial agents. We believe that such a good cycle can be realized.