Overview of the antibacterial R&D

landscape in Japan

Norio Ohmagari, M.D., M.Sc., Ph.D.
Director, Department of Infectious Diseases
Director, AMR Clinical Reference Center
Director, Disease Control and Prevention Center
Director, WHO Collaborating Centre for Prevention,
Preparedness and Response to Emerging Infectious
DiseasesNational Center for Global Health and Medicine
E-mail: nohmagari@hosp.ncgm.go.jp
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Contents• Movement• Private, Academia, and Government• Progress• Regulatory, Pipeline, and Incentives• Barriers

2History of the Development of Antimicrobial Agents in Japan

Japanese Journal of Chemotherapy VOL. 65 NO. 2 3P149

Movements in Japan• 2013: The Committee of Promotion of Drug Discovery was launched in theJapanese Society of Chemotherapy for facilitation of development of newantimicrobial agents.
• 2014: Statement from the Committee of six academic societies, requiring
facilitation in the development of new antimicrobial agents was submitted to theMinister of Health, Labour and Welfare, the Minister of Education, Culture, Sports,
Science and Technology, and the Minister of Economy, Trade and Industry.
• 2016: The Committee of eight academic societies issued document: “Measures
Against Antibiotic-Resistant Bacteria Through Global Cooperation”
4Movements in Japan• April 2016: The Japanese government announced the “National Action Plan
on Antimicrobial Resistance (AMR)”
Major Items regarding R/D:
1.

Research to facilitate R/D

2.

Promotion of industry-government-academia collaboration

3.

Formulation of international clinical evaluation guidelines, etc.

4.

Priority review system for antimicrobials

5.

Collaboration with global funding agencies
5Movements in Japan• April 2017: The Japan Pharmaceutical Manufacturers Association (JPMA)
submitted the Suggestion of Measures to R/D to Ministry of Health, Labour andWelfare
Suggestions:1.

Stockpile/purchase system of new drugs

2.

Establishing funds, and R/D organization (consortium) through PPP

3.

Formulation of international common clinical evaluation guidelines forfacilitation of the clinical development of new drugs
4.

Market Entry Rewards

5.

Preliminary drug price review system based on drug profiles

6Movements in Japan• June 2019: The JPMA submitted “Suggestion from the pharmaceuticalindustry on the introduction of Pull incentive towards facilitation of theresearch and development of drugs, etc. for AMR” to the Minister of Health,Labour and Welfarea.

Market Entry Rewardsb.

Transferable Exclusivity Extensions

7

Progress

8

Regulatory

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International Harmonization• The Pharmaceuticals and Medical Devices Agency (PMDA)
participates in the tripartite meeting of the FDA/EMA/PMDA: A

review is being conducted to formulate common clinical study
guidelines through meetings between Japanese, US and European
regulatory authorities• Revision of the guideline for the method of clinical evaluation of
antimicrobial agents10

SAKIGAKE Designation System• Scheme for rapid approval• Scheme for rapid authorization of unapproved drug via the councilon unapproved drug/ Off label use to meet unmet needs

11Scheme for rapid approval

Privilege for innovative drug in urgent need:
1) Prioritized Consultation [Waiting time: 2 months→1 month]
2) Pre-application Consultation
3) Prioritized Review [12 months → 6 months]

12Scheme for rapid authorization via the council on unapproved drug/ Off label use to meet unmet needs -13

Pipeline14

Product nameor descriptor Pre-clinical
Company/Institution (ID if available) development stage Product type

Product typemoreinformation(please choosefrom the list inthemethodology) Spectrum

Mode ofaction

Bacterial

Shionogi

anti-GNbacteria
program 1

Curative treatment: directly
acting small molecule
Lead optimization antibacterial agents

Shionogi

anti-GNbacteria
program 2

Curative treatment: directly
acting small molecule
Lead optimization antibacterial agents

Hisamitsu

Wakunaga

besifloxacinhydrochloride Unknown

WFQ228Pre-clinicalcandidate

Curative treatment: directly
acting small molecule
antibacterial agents

Curative treatment: directly
acting small molecule
antibacterial agents

Curative treatment: directly
acting small moleculeDaiichi SankyoDS86760016
antibacterial agents
Curative treatment: directlySumitomo Dainippon anti-bacterial
acting small molecule
Pharmatherapies
Lead optimization antibacterial agents
Pre-clinicalcandidate

Single agent

Gram-negative (WHOcritical priority
Beta-lactam
pathogens – at least one)antibiotic

Single agent

Gram-negative (WHOcritical priority
Beta-lactam
pathogens – at least one)antibiotic

Single agent

Gram-positive (WHOpriority pathogens – atleast one)DNA
topoisomerase II inhibitor;DNA
topoisomeras
e IV inhibitor

Single agent

DNA
topoisomerase II inhibitor;
Gram-negative (WHODNA
critical priority
topoisomeras
pathogens – at least one)e IV inhibitor

Single agent

Gram-negative (WHOLeucyl-tRNA
critical priority
synthetasepathogens – at least one)inhibitor

Single agent

Unknown

15Unknown

Product nameor descriptor Pre-clinical
Company/Institution (ID if available) development stage Product type
Tuberculosis

Product typemoreinformation(please choose
from the list inthemethodology) Spectrum

Mode ofactionTB

Shionogi

S-004992

IND enablingstudies

Shionogi

antimycobacterialtherapies

Curative treatment: directly
acting small molecule
Lead optimization antibacterial agents

Single agent

antimycobacterial
therapies

Curative treatment: directly
acting small molecule
Lead optimization antibacterial agents

Single agent

Targeted pathogenspecific (WHO priority
pathogens, TB or C.
difficile)
Targeted pathogenspecific (WHO priority
pathogens, TB or C.
difficile)
Targeted pathogenspecific (WHO priority
pathogens, TB or C.
difficile)

Biologic

TypeIII
Gram-negative (WHOsecretion
critical priority
systempathogens – at least one)inhibition

TakedaBiochemicalShionogi

COT143

Chiome Bioscienceanti-infectious
diseasesThyas

anti-infectiousdiseases

Curative treatment: directly
acting small molecule
antibacterial agents

Single agent

Curative treatment: directly
Pre-clinicalacting large molecule
candidate
antibacterial agents
Curative treatment: directly
acting large molecule
Lead optimization antibacterial agents
Curative treatment: directly
acting large molecule
Lead optimization antibacterial agents

Biologic

Biologic

Unknown

Unknown

Cell wall
synthesis
inhibition

Unknown

Unknown

Monoclonal
antibody

Cellulartherapy16

Product typemore
information
Spectrum(please(moreProductchoose fromdetailed
name orthe list ininformati
descriptor Pre-clinicaltheon)
Company/Instit (ID ifdevelopment
methodolog Spectru (ifutionavailable) stage
Product typey)mavailable) Indication
Curative treatment: directlyAspergillu
antifungal Leadacting small molecule
Unspecifi s,Fungal
Shionogi
program 1 optimization antibacterial agents
Single agent ed
Candida infection
Curative treatment: directlyAspergillu
antifungal Leadacting small molecule
Unspecifi s,
FungalShionogi
program 2 optimization antibacterial agents
Single agent ed
Candida infection
IND enablingstudies(commencement ofCurative treatment: directly
human
acting small molecule
Unspecifi
FungalEisai
E-1210testing)
antibacterial agents
Single agent ed
infection
IND enablingstudies(commencement ofCurative treatment: directlyToyama
humanacting small molecule
Unspecifi
FungalChemical
T-2307
testing)
antibacterial agents
Single agent ed
infection

Mode of action--

Unidentified pharmacologicalactivity

Unidentified pharmacologicalactivity

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Incentives

18

AMR
consortium:
Not yet

19

20

21

22

Pull incentives

Although proposed…
• Market Entry Rewards• Transferable Exclusivity Extensions

23

Barrier• Lack of incentives, especially Pull incentive• Access to essential antimicrobials; shortage of cefazolin

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https://www.amed.go.jp/en/program/list/01/06/005.html

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