A narrative review on drug development for the management of antimicrobial- resistant infection crisis in Japan: the past, present, and future

ABSTRACT

Introduction

Antimicrobial resistance (AMR) is a major threat to global health requiring continuous development of new antimicrobial agents. Antimicrobial research and development (R&D) should be promoted in the pharmaceutical industry and academia to ensure sustainable patient access to new treatment options and reduce the global AMR burden.

Areas covered

This review describes the historical challenges in novel antimicrobial drug development in Japan, current national efforts to promote the development, and proposals to effectively manage future AMR pandemics. Literature searches were performed in the PubMed database (from inception to January 2022).

Expert opinion

R&D activities in the antimicrobial space in Japan have been insufficient due to multiple factors, including unfavorable cost-profit balance and differences in regulatory requirements between Japan and Western countries. However, the situation is improving with the implementation of the Japanese AMR action plan, drug R&D programs led by the Japan Agency for Medical Research and Development, and efforts of regulatory agencies in the United States, Europe, and Japan in aligning and expediting the clinical development process. Further actions during the interpandemic period will strengthen antimicrobial R&D, including international and interdisciplinary collaboration, continued funding and investment with the national government’s leadership, and fostering of new-generation academic research leaders.

PLAINLANGUAGE SUMMARY

Every year, many people suffer and die of antimicrobial-resistant infections worldwide. New treatment options are required to tackle antimicrobial-resistant infections; however, pharmaceutical companies have not been very active in developing antimicrobial agents in the last two decades. This was mainly due to the difficulty in discovering new and effective compounds and insufficient funds being spent on drug discovery. In addition, differences in drug development requirements between the United States (US), Europe, and Japan have made it difficult for Japanese pharmaceutical companies to develop antimicrobial agents that can be used in all regions in a timely manner. In the last decade, several measures have been taken to re-activate antimicrobial research and development in the pharmaceutical industry, as well as in academia, in Japan. These measures include a national action plan to combat antimicrobial-resistant infections and research support programs led by the Japan Agency for Medical Research and Development. Regulatory authorities in the US, Europe, and Japan have initiated efforts to expedite the development of drugs to treat infections. Moreover, pathways for accelerated regulatory review have been established to reduce the time taken for new drugs to be approved, and this has already been applied to several new anti-infective drugs. To combat the coronavirus disease 2019 (COVID-19) pandemic, the development of novel vaccines and antiviral drugs has been accelerated with unprecedented speed. Additional actions, such as international research collaboration programs and investment in new antimicrobial development, may help promote antimicrobial research and development activities in Japan.

KEYWORDS:

• Antimicrobial resistance
• crisis management
• drug development
• interdisciplinary collaboration
• market failure
• multiregional clinical trials
• national action plan
• public health
• regulatory science

Article highlights

• The high global burden of antimicrobial resistance (AMR) underscores the need for reviving antimicrobial research and development (R&D) activities in the pharmaceutical industry and academia to ensure robust patient access to new treatment options.

• Although the Japanese pharmaceutical industry has faced difficulties in developing novel antimicrobial agents in a timely and globally harmonized manner, the situation has improved in the last decade owing to differences in the antimicrobial agent R&D landscapes and regulatory requirements across countries or regions.

• In Japan, national efforts to promote antimicrobial R&D have been initiated, such as the AMR National Action Plan and research support programs hosted by the Japan Agency for Medical Research and Development.

• Robust funding and investment in antimicrobial research through international platforms and the national government’s leadership can facilitate the development of novel antimicrobial agents.

• Lessons learned from the unprecedented/accelerated vaccine and antiviral drug development for coronavirus disease 2019 are applicable to novel AMR drug R&D activities among pharmaceutical companies, government, and academia.

• To effectively manage future AMR pandemics, pandemic preparedness, establishment of crisis management systems, and interdisciplinary collaboration among the government, regulators, academia, and pharmaceutical industry are essential.

• Talent development to foster new-generation academic research leaders during the interpandemic period is eagerly anticipated.

Acknowledgments

Medical writing and editorial assistance were provided by Mami Hirano, MS, of Cactus Life Sciences (part of Cactus Communications) and funded by Pfizer Japan Inc.

Declaration of interest

T Ohashi is a full-time employee of Pfizer Japan Inc. M Nagashima and N Kawai are full-time employees of Pfizer R&D Japan. T Ohashi and M Nagashima hold stocks and stock options from Pfizer Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Additional information

Funding

This work was supported by Pfizer Japan Inc., who provided support for medical writing and article processing charges for the present manuscript.