AMR Benchmark Opportunities: progress update

Research-based pharmaceutical company

Shionogi & Co, Ltd
This table is part of a November 2023 report that looks at what actions each company in scope of the Antimicrobial
Resistance (AMR) Benchmark has taken with regards to each of the Opportunities set out in its 2021 AMR Benchmark
Report Card. The full 2021 Report Card is also included in this PDF.

2021 O PPO RTU N IT Y

2023 U PDATE

What was the Opportunity shared in the AMR Benchmark?

What progress has been made on this Opportunity?

Expand breadth of R&D pipeline and depth of R&D

Shionogi has expanded the breadth of its AMR pipeline toaccess and stewardship plans.

include more pathogens.

Shionogi has one of the most diverse pipelines across all

For olorofim (F901318), a novel oral antifungal therapy

large research-based companies in the AMR Benchmark. It

developed by F2G to treat invasive aspergillosis, thecan expand the focus of its pipeline to target resistant path-company will be conducting clinical trials and subsequentogens for which R&D is limited, such as Campylobacter spp.

registration and commercialisation in Europe and Asia. This

and H. pylori. For its recently approved cefiderocol (Fetroja/

project is currently in Phase III of clinical development.

Fetcroja), Shionogi engages with generic medicines manu-

In July 2023, Shionogi acquired Qpex, a company

facturers and access-related organisations such as GARDP

developing two combination products targeting resistantand the Clinton Health Access Initiative to increase afforda-

gram-negative pathogens. These products, designed forbility and availability. Shionogi can intensify these engage-both oral and IV administration, are based on xeruborbac-

ments to reach more patients and countries. Shionogi cantam, a novel boronic acid ß-lactamase inhibitor, and focus

continue to build towards a comprehensive surveillanceon pathogens like carbapenem-resistant A. baumannii, P.

programme to ensure cefiderocol is not used excessively.

aeruginosa, and Enterbacterales.
For more details about the collaboration progress
between Shionogi, Global Antibiotic Research andDevelopment Partnership (GARDP) and Clinton Health
Action Initiative (CHAI) to ensure access and stewardshipfor cefiderocol, please refer to update below.

Expand registration to cefiderocol (Fetroja/ Fetcroja) in

In June 2022, Shionogi, GARDP and CHAI engaged in aaccess countries.

three-way collaboration agreement which aims to roll out

Shionogi can file cefiderocol (Fetroja/ Fetcroja) for reg-

cefiderocol, while ensuring quality assurance and appropri-

istration in access countries. Further, to accelerate theate use. This collaboration also strives to develop real-world

availability of cefiderocol in access countries Shionogi canbest practices on how access can be achieved. Together

consider voluntary non-exclusive licensing, compassionate

with this collaboration agreement, Shionogi and GARDP

use programmes and public/private partnerships.

signed a first-in-kind and publicly available license and technology transfer agreement for cefiderocol. This agreement
encompasses the development, registration, manufacturing
and commercialisation of the product. The license territory
covers 135 countries including all low-income countries andmost lower-middle and upper- middle income countries. To
increase affordability, Shionogi has waived its cost recoupment fees on cefiderocol sales in low-income and lower
middle-income countries.
In September 2023, GARDP entered into a sublicensing
agreement with Orchid Pharma for the manufacturingof cefiderocol. The sublicence agreement stipulates that
Orchid Pharma will submit the product to the World HealthOrganization’s (WHO) medicines prequalification (PQ)
programme. In March 2023, the WHO PQ Unit publishedthe first invitation to manufacturers of medicinal products
for treatment of multi-drug resistant bacterial infections, tosubmit an Expression of Interest (EOI) for product evaluation of cefiderocol.

24AMR Benchmark Opportunities: progress update

Research-based pharmaceutical company

2021 O PPO RTU N IT Y

2023 U PDATE

What was the Opportunity shared in the AMR Benchmark?

What progress has been made on this Opportunity?

Expand adaptations to brochures and packaging toShionogi did not report any further adaptations to bro-consider more patient needs.

chures and packaging for its marketed antibiotics.

Shionogi adapts brochures to take account of paediatricuse to support the appropriate use of cefcapene pivoxil(Flomox) by patients. It can further adapt its brochures
and packaging of all antibacterial and antifungal medicines
to consider local languages, literacy levels, environmental
conditions and patient adherence to treatment.
Publicly share raw data from surveillance programmes.

Shionogi has shared the anonymised raw data from theShionogi runs the multinational SIDERO-WT programme,

SIDERO-WT programme to the AMR Register, an initiative

which is focused on resistance against antibacterials tar-by Vivli.

geting Gram-negative bacteria. It can publicly share raw

As with all datasets available on AMR Register, the data-

data from this surveillance programme, following throughset is available for researchers to access after submitting aon commitments to share this with the AMR Register inrequest, which is then subjected to a review by Vivli and the2021. Additionally, either Shionogi or the managing partners

relevant company before data is shared.

should publicly share raw data from the other surveillance
programmes it is involved in.

Data from the other four surveillance programmes
Shionogi is involved in, have not been shared with the AMR
Register, nor has the company reported public disclosure of
the raw data from these programmes.

25

Antimicrobial Resistance Benchmark 2021

SNG

Overall Performance
2020

2021

63% 58%▼

Access to Medicine Foundation

Shionogi & Co, Ltd
Large R&D-based pharmaceutical company
Stock exchange: TSE • Ticker: 4507 • HQ: Osaka, Japan • Employees: 5,233

SNG
PERFORMANCE
Shionogi performs average overall in its evaluated Research Areas

Performance in the Benchmark

0%compared to the other large research-based pharmaceutical companies
in scope.
R&D: Shionogi performs well in R&D. Eight of its 11 projects target
critical and/or urgent pathogens. For the first time Shionogi has a
vaccine in their pipeline. Shionogi is working on improving access andstewardship of its antibacterial cefiderocol.
Responsible Manufacturing: Shionogi leads. Reports comprehensiveof strategy and compliance

Stewardship: Performs well. It fully decouples incentives for sales
agents from sales volumes. It publicly shares aggregated results of its
surveillance programmes. It reports comprehensive conflict of interest
mitigation for its educational programmes. It adapts brochures forpatients.

50%

100%

Points70%

R&D

21/ 3093%

Manufacturing

14/ 15

4%

Access

1/ 25

80%

Stewardship
0%50%

16/ 20100%

How Shionogi was evaluatedAppropriate Access: Performs low. Its relevant on- and off-patentproducts are not available in access countries.

52/ 90

Performance by Research Area

environmental risk-management strategy for own sites and suppliers;
co-leads in compliance with limits at own sites; leads in public disclosure

Points58%

Overall score

A R&D

1

2.1 2.2 2.3 2.4

3

●

●

●

●

1

2

3

B Manufacturing ●

●

●

●

●

1.1

1.2 1.3 2.1 2.2 2.3

3

C Access

●

●

●

4

5

6

7

C Stewardship

●

●

●

●

●

●

●

●

● ● ● Scored●

Not scored

OPPORTUNITIES FOR SHIONOGICHANGES SINCE 2020

Expand breadth of R&D pipeline and depth of R&D access and stewardship plans. Shionogi• In response to an opportunity from the 2020

has one of the most diverse pipelines across all large research-based companies in the AMR

AMR Benchmark, in July 2021, Shionogi

Benchmark. It can expand the focus of its pipeline to target resistant pathogens for which R&D isentered into a collaboration with the Global

limited, such as Campylobacter spp. and H. pylori. For its recently approved cefiderocol (Fetroja®/

Antibiotic Research and Development

Fetcroja®), Shionogi engages with generic medicines manufacturers and access-related organiza-

Partnership (GARDP) and the Clinton

tions such as GARDP and the Clinton Health Access Initiative to increase affordability and availabil-

Health Access Initiative (CHAI) to accelerate

ity. Shionogi can intensify these engagements to reach more patients and countries. Shionogi canaccess, including in LMICs, to the antibiotic

continue to build towards a comprehensive surveillance programme to ensure cefiderocol is not
used excessively.

cefiderocol.
• In October 2020, Shionogi expanded invest-

Expand registration to cefiderocol (Fetroja®/ Fetcroja®) in access countries. Shionogi can file cefi-

ments into vaccine development through aderocol (Fetroja®/ Fetcroja®) for registration in access countries. Further, to accelerate the availabil-licensing partnership agreement with HanaVax

ity of cefiderocol in access countries Shionogi can consider voluntary non-exclusive licensing, com-

for research, development, manufacturing, dis-passionate use programs and public/private partnerships.

tribution and commercialisation of their S.

Expand adaptations to brochures and packaging to consider more patient needs. Shionogi adapts

pneumoniae nasal vaccine candidate.

brochures to take account of paediatric use to support the appropriate use of cefcapene pivoxil• In its 2020 Environmental Report, Shionogi(Flomox®) by patients. It can further adapt its brochures and packaging of all antibacterial and anti-

discloses compliance with limits of its own andfungal medicines to consider local languages, literacy levels, environmental conditions and patient

suppliers’ sites, some details of audit results

adherence to treatment.

and some names and/or locations of its suppli-

Publicly share raw data from surveillance programmes. Shionogi runs the multinational
SIDERO-WT programme, which is focused on resistance against antibacterials targeting Gram-ers and sole waste contractor.
• In 2020, Shionogi started to support thenegative bacteria. It can publicly share raw data from this surveillance programme, following

SENTRY programme for the surveillance ofthrough on commitments to share this with the AMR Register in 2021. Additionally, either Shionogi

cefiderocol. The results are shared publicly via

or the managing partners should publicly share raw data from the other surveillance programmes it

open-access journal articles and the SENTRY

is involved in.

website.

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Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

SALES AND OPERATIONS

SNGRevenue by business segment

Therapeutic areas: Infectious diseases, Psycho-neurological diseases

2019

Business segments: Prescription drugs

2020

Product categories: Generic medicines, Innovative medicines, Vaccines

An Shionogi Company Ltd

297,177
0

M&A since 2020: In July 2020, Shionogi entered into agreement with Ping
An Life Insurance of China, Ltd. to establish of a joint venture called Ping

333,371

100,000

200,000

300,000

400,000

Prescription drugs

500,000
mn JPY

SNG
Revenue by region
109

2019
95

2020
0
Japan

31
25

100

200
bn JPY

Rest of world

PIPELINE for pathogens in scope

PORTFOLIO for pathogens in scope

Pipeline size: 11 projects targeting pathogens in scope* (8 antibacterial

Comparatively small portfolio: At least 8 products: 8 antibacterial

medicines; 1 antibacterial vaccine; 2 antifungal medicines).

medicines

Development stages: 5 discovery programmes for antifungals, antituber-On-patent medicine: 1 (cefiderocol)

culosis and antibacterial candidates; 2 preclinical projects including an anti-

Off-patent/generic medicines: 7 of which 2 were selected for analysis*

body against P. aeruginosa and a vaccine for S. pneumoniae; and 1 Phase II(cefcapene [W], flomoxef [W])adaptive project.

AWaRe medicines**: 2 Access group; 5 Watch group

Novelty: 0 novel clinical-stage medicine projects.
‘Critical’ and/or ‘urgent’ pathogens: 8 projects, cefiderocol (Fetroja®/
Fetcroja®) and its adaptations target CRAB, CRE and CRPA. Furthermore,
Shionogi has discovery/preclinical projects targeting C. auris and P.
aeruginosa.
Regulatory approvals: 3 approvals. In November 2019, cefiderocol (Fetroja®/Fetcroja®) was approved by the FDA for the treatmentof complicated urinary tract infections (cUTIs), including pyelonephri-

SNG
Pipeline for priority pathogens
01
0rial pneumonia (HABP/VABP). In April 2020 the EMA approved cefider-

2
10

20

● Antibacterial vaccine● Antibacterial medicine● Antifungal vaccine● Antifungal medicine

SNG
Products on the market

tis. In September 2020, the FDA approved the supplemental indication
for the treatment of hospital-acquired and ventilator-associated bacte-

8

8
0

10

20

● Antibacterial vaccine● Antibacterial medicine● Antifungal medicine

ocol (Fetroja®/Fetcroja®) for the treatment of gram-negative bacterial
infections.

PERFORMANCE BY RESEARCH AREAA

RESEARCH & DEVELOPMENT Evaluated: medicine & vaccine pipelines for priority* bacteria & fungi

A.1

Highest relative investment in R&D

invested USD 74.22 mn in R&D for antibacterial

other companies who reported investments toShionogi discloses to the Benchmark its R&D

and antifungal medicines and vaccines in 2019

the Benchmark.. Shionogi has pledged USD 20

investments during 2019 and 2020 in antibac-

and 2020. Shionogi invests the highest propor-

mn to the AMR Action Fund over the next ten

terial and antifungal medicines and/or vaccinestion of its revenues in R&D in this area and theyears.

for pathogens in scope. Shionogi reports that it

third highest absolute amount compared to the

Pipeline targeting priority pathogens: 11 As at 24 September 2021
Discovery

Pre-clinical

Antituberculosis
programme 1

Antibody [P. aeruginosa]

Antituberculosis
programme 2♦ S. pneumoniae vaccine

Antifungal
programme 1
Antifungal
programme 2
Antibacterial
programme 3* See Appendix V for information about
eligibility for R&D projects and Appendix
VII for eligibility criteria of products.
** Listed on the 2019 WHO EML.

Phase I

Phase II
Fetroja®/Fetcroja® additional population:
paediatricPhase III

ApprovalCefiderocol (Fetroja®/
Fetcroja®)[FDA; Nov-19] cUTI
[Enterobacteriaceae][EMA; Apr-20]
Gram-negative bacterial
infections[FDA; Sep-20] HABP/
VABP [Enterobacteriaceae]♦ Vaccine
cUTI = Complicated urinary tract infection
HABP = Hospital-acquired bacterial pneumonia
VABP = Ventilator-associated bacterial pneumonia

135

Antimicrobial Resistance Benchmark 2021

Access to Medicine Foundation

A.2.1 Medium-sized diverse pipeline

the extension of its indication to treat children.

The company reports 11 projects targeting path-

Cefiderocol does not meet any of WHO’s innova-

ogens in scope: ten medicines and one vaccine,

tiveness criteria.

nine targeting bacterial pathogens and two tar-

A.3

Plans to improve access and stewardshipfor cefiderocol

Shionogi has four projects in its late-stage pipeline, all related to different indications of thegeting fungal pathogens. Out of the 11 projects,

A.2.3 Newly active in vaccine development

same compound, cefiderocol, first marketed infive are in discovery stage, two are in preclinical

Shionogi reports one innovative vaccine projectDecember 2019.

development, one is in clinical development andin its pipeline. It consists of a preclinical vaccine

Shionogi reports having an ongoing Global

three received marketing approval during thecandidate against S. pneumoniae developed inCompassionate Use programme for cefidero-

period of analysis.

collaboration with HanaVax Inc.

col. It is discussing a potential technology trans-

A.2.2 No clinical-stage novel projects

A.2.4 Investing in early stage programmes tar-fer agreement with generic medicine manufacgeting critical and/or urgent priorities

Shionogi’s clinical-stage medicine pipeline con-turers to extend access to cefiderocol to other
territories. It is also building partnerships withsists of one innovative R&D medicine, cefider-

Shionogi has eight projects targeting pathogens

not-for-profit organisations to build a systemocol, a siderophore cephalosporin antibacterial

defined as ‘critical’ by WHO’s list of priority path-to support stewardship of cefiderocol. Shionogi

for the treatment of multi-drug resistant infec-

ogens and/or characterised as ‘urgent’ threats

reports plans to conduct surveillance of cefider-tions. Cefiderocol (Fetroja®/ Fetcroja®) obtainedby the US Centers for Disease Control andocol. Shionogi applied for the inclusion of cefi-

marketing approval for the treatment of com-

Prevention (CDC). Cefiderocol, which accounts

derocol in the WHO’s EML and suggested includ-plicated urinary tract infections (cUTIs), includ-for four of these projects, targets several MDR

ing it in the Reserve (AWARE) category.

ing pyelonephritis, from the FDA in November

gram-negative pathogens such as A. bauma-

2019, and for HABP/VABP in September 2020.

nii and Carbapenem-resistant/ESBL-resistant

In April 2020, it received approval from theEnterobacteriaceae. Shionogi is carrying out

EMA for the indication of gram-negative bacte-

several discovery and preclinical programmes

rial infections. Cefiderocol is in Phase II trials fortargeting P. aeruginosa and C. auris.

B

RESPONSIBLE MANUFACTURING Evaluated: antibacterials manufacturing (APIs and drug products)

B.1

Comprehensive environmental risk-man-limits.

flomoxef (Flumarin®), doripenem (Doribax®) andagement for own sites and suppliers;

Shionogi expects its only external private

sulfamethoxazole/trimethoprim (Bakuta®), aretracks compliance with limits at own

waste-treatment plant to comply with its gen-compliant with discharge limits. It also publishes

sites and supplierseral environmental standards. It audits this planta table listing its antibacterials in scope, their

Shionogi reports a comprehensive strategy toevery year which includes the suitability of tech-connection to own sites and suppliers, and which

minimise the environmental impact of waste-nologies used for processing waste and pro-are compliant with discharge limits. Further, itwaters and solid waste from antibacterial man-tocols for preventing contamination. All solid

publishes where five of its suppliers in scope

ufacturing at its sites, including audits every fivewaste and wastewater sent to this plant is set toare located (Japan and India) and the respective

years. It reports setting discharge limits in the

be incinerated.

products supplied by each. The name of its only

receiving environment for all antibacterials manufactured at its site, based on PNECs to limit
AMR, as recommended by the AMR Industry
Alliance, or the EMA. It also reports quantify-

external private waste-treatment plant in scope
B.2

Publicly discloses information on envi-

is also disclosed.

ronmental risk management; aggregatedaudit results and compliance with limits

B.3

System in place to maintain production
quality for own and suppliers’ sites; noing discharge levels at its site using a mass bal-

Shionogi leads in public disclosure of its envi-

ance approach, verified by chemical analysis ifronmental risk-management strategy. It pub-requests for official corrective action

applicable. Its sole manufacturing site in scope

lishes some information on audit results, based

Shionogi reports that its own sites and suppliers

is reported to be fully compliant with discharge

on its ERM strategy, and covers wastewater

have a system to maintain high-quality antibac-

limits.

management, solid waste management and dis-terial production consistent with international

Shionogi requires third-party suppliers ofcharge limits. It is a member of the AMR Industry

GMP standards. This includes periodic risk-

antibacterials to follow the same standards,

Alliance, which publishes a list of recommended

based audits and tracking of corrective and pre-including limits based on PNECs. It reports

antibacterial discharge targets. It publicly dis-

ventive actions. Shionogi also requires its suppli-

conducting on-site audits every five years. It

closes that all 5 antibacterials manufactured at

ers to audit their own suppliers. The Benchmark

requests and reviews the discharge levels of its

its own site are compliant with discharge limits.

found no requests for official corrective action

suppliers. It also reports five out of nine supplier

In addition, it is publicly disclosed that five out

from the FDA or EMA related to non-conform-sites have quantified discharge levels and three,of nine supplier sites have quantified discharge

ities with cGMP at Shionogi’s own sites or any

or 33%, of those are compliant with discharge

levels and three, or 33%, of those, which supply

subsidiaries that manufacture antibacterials.

C

APPROPRIATE ACCESS & STEWARDSHIP – ACCESS

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries***
Shionogi is not eligible for indicators: C.1.3 andnegative bacteria when there are few treatment

treat several bacterial infections, in one accessC.2.3. For more information, see Appendix VII.

options available. It was approved by the FDA in

country (China).

2019 . Cefiderocol is newly included in the WHO
C.1.1

No filings for relevant on-patent

22nd EML (2021) as a ‘Reserve’ group antibiotic

medicines

effective against multi-drug resistant bacteria.

Shionogi’s performance is low as it has not yet
filed its relevant on-patent medicine in accesscountries. Its relevant on-patent medicine is

C.1.2 Limited filings for relevant off-patent
medicines

the antibiotic cefiderocol (Fetroja®/Fetcroja®),

Shionogi’s performance is low. It filed its off-pat-

used to treat infections caused by aerobic Gram-ent antibiotics flomoxef and cefcapene, used to*** 102 low- and middle-income countries where better access to medicine ismost needed.

136

Antimicrobial Resistance Benchmark 2021

C.2.1 No access strategy for relevant on-pat-

Access to Medicine Foundation

C.2.2 Expanding access to off-patent/genericent medicine

medicines

in July 2021, GARDP identified flomoxef as apotential treatment option for neonatal sepsis.

Shionogi’s performance is low as it does not

Shionogi’s performance is low as it does notreport strategies to expand access to its relevant

provide access to its two relevant off-patent/

C.3

on-patent medicine in access countries during

generic antibacterial medicines, flomoxef andShionogi’s performance is low as it does not yet

the period of analysis. However, in July 2021,

cefcapene, in access countries. These two med-

make its relevant products available in access

Shionogi, GARDP and CHAI announced a MOU toicines did not meet all regulatory requirements

countries.

accelerate access to cefiderocol in low- and mid-because their respective clinical trials were con-dle-income countries.

ducted prior to the ICH guidelines. Shionogi does

No supply in access countries

not actively promote these medicines. However,C

APPROPRIATE ACCESS & STEWARDSHIP – STEWARDSHIP

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally
C.4

Comprehensive COI mitigation strategies

antibacterial and/or antifungal medicines. Its

in place for its educational programmesmarketing materials reflect emerging resist-

Shionogi performs strongly in conflict of interest

ance trends and/or include treatment guide-(COI) mitigation for the five AMR-related edu-

lines for healthcare professionals: for cefiderocol

Shionogi is active in multiple AMR surveil-

cational programmes for HCPs assessed by the(Fetroja®/Fetcroja®), doripenem (Finibax®) andlance programmes. It runs the multinational

Benchmark. To mitigate COI for one programme,

flomoxef (Flumarin®).

SIDERO-WT programme, which is focused on

it provides financial resources to an independ-

C.7

Active in multiple AMR surveillance programmes; openly publishes aggregatedresults

resistance against Gram-negative bacteria in
Makes one type of brochure and/or

13 countries and has been running since 2014.

gramme. The remaining four programmes havepackaging adaptation to facilitate appro-

Shionogi only shares the aggregated results

all three COI mitigation strategies looked for by

priate use by patients

through peer-reviewed open-access journal arti-

ent third party (Radio Nikkei) to develop the pro-

C.6

the Benchmark: (1) content is developed inde-

Shionogi adapts brochures to facilitate thecles, however, within 2021, it is planning to sharependently from its marketing department; (2) aappropriate use of cefcapene pivoxil (Flomox®)

the raw data on the AMR Register, an open-ac-

pledge not to provide financial or material incen-

by patients. Shionogi is middle-performing incess data platform. For the remaining pro-tives to participants; and (3) it does not use

this measure, taking account of paediatric use.

grammes, the aggregated results are sharedbranded materials.

It has created a brochure that is easy to under-

through peer-reviewed open-access journal arti-

stand using simple illustrations, which is tailoredcles, as well as on an open-access data platform

Fully decouples incentives for sales

to the treatment of children to improve paedi-

for the SENTRY programme (a programme man-agents from sales volumes, and engages

atric use.

aged by JMI laboratories).

C.5

in marketing practices to address appropriate use
Shionogi performs strongly in sales practices.
It reports that it fully decouples incentives forsales agents from sales volumes of its antibacterial and/or antifungal medicines.
Shionogi engages in marketing practices
that aim to address the appropriate use of its

137