ANTIMICROBIAL RESISTANCE (AMR) PROGRAMME

How can pharma get the few
promising drugs in development
to patients battling superbugs?
MAY 2024

In the race to create replacement antibiotics and antifungals to combat
superbugs, we are falling dangerously short, putting people all over theworld at risk. But with a fundamental shift in research and development(R&D), including investment in access and stewardship, there is an
opportunity to stop drug resistance in its tracks. This report shows
how this can be achieved by examining key antimicrobials in late-stage
R&D that target some of the most severe drug-resistant pathogens. If
patients globally were able to access these promising antibiotics andantifungals, at least 160,000 lives could be saved from drug-resistantinfections each year. By highlighting what can be done with what iscurrently in the pipeline, this report sets out ways in which companies
can develop sustainable solutions amid the seemingly losing battle
against this global health threat.

Antimicrobial research & development

ACKNOWLE DG E M E NTS

The Access to Medicine Foundation would like to thank the following
people and organisations for their support..
FU N D E RS

The UK Foreign, Commonwealth and Development Office
The Dutch Ministry of Health, Welfare and Sport
The Wellcome Trust
AXA Investment Managers
Stewart Investors

AUTH O RS

E D ITO R IAL TE AM

E XPE RT R E VI E WE RS

Martijn van Gerven

Jana Jacobs

Sabiha Essack, Antimicrobial Research Unit,

Marijn Verhoef

University of KwaZulu-NatalClaudia Duarte

Valeria Gigante, World Health Organization

Emily Gauruhn

ACCESS TO M E D I CI N E FO U N DATI O N

The Access to Medicine Foundation is an independent non-profit
organisation that seeks to transform the healthcare ecosystem
by motivating and mobilising companies to expand access to theiressential healthcare products in low- and middle-income countries.
Naritaweg 227-A
1043 CB, Amsterdam
The Netherlands
For more information about this publication, please contact
Marijn Verhoef, Director of Operations and Researchmverhoef@accesstomedicinefoundation.org+31 (0) 20 215 35 35
www.accesstomedicinefoundation.org

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Access to Medicine Foundation

Table of contents

4

About this report

5

Executive summary

7	Introduction
When the drugs don’t work
12

Access and stewardship during R&D

	From pipelines to patients
16

Analyis: company case studies

	Assessing the five selected projects
28

Analysis: wider R&D landscape
Are funders promoting access and stewardship planning?

31	Key findings
Structured advance planning for access and stewardship has not become
the norm yet
33	Spotlight
Without the resources and efforts of big pharma, innovation might neverreach all eligible patients sustainably
34	Recommendations
Prioritising access and stewardship: How to rethink and redesign R&D
36

List of abbreviations

38	Definitions
40

References3

Antimicrobial research & development

About this paper
This report is part of the Access to Medicine Foundation’s Antimicrobial Resistance(AMR) Programme, which works to mobilise pharmaceutical companies in responding to the growing challenge of drug-resistant infections. The AMR Programme’s
publications – including both the AMR Benchmark (published in 2018, 2020 and2021) and targeted thematic reports such as this – focus on how pharmaceuticalcompanies perform in terms of acting on identified priorities to address AMR.
HOW TH IS RE PO RT WAS D EVE LO PE D
The case studies, discussion and recommendations in this report have been drawn
from companies’ pipeline verification process for the upcoming 2024 Access to
Medicine Index, research published in the 2021 AMR Benchmark, as well as fromrecent interviews with selected companies. Consultations were also held with relevant expert stakeholders, including funder and partner organisations working tosupport antimicrobial R&D. The report was further informed by sources available
in the public domain, including peer-reviewed literature, company and global healthreports, policy literature and government documents. The information collectedfrom the sources was cross-checked to ensure accuracy, including directly withcompanies and other stakeholders, as appropriate and relevant.
SCO PE O F TH E RESE ARCH
Companies
In identifying a combination of large and small companies, as well as latestage (Phase II and onward) antibacterial and antifungal projects, two (2)large research-based pharmaceutical companies (GSK and Pfizer) and three(3) small- and medium-sized enterprises (SMEs*: F2G, Innoviva Speciality
Therapeutics and Venatorx Pharmaceuticals) were selected for case studies. In addition, 25 other companies are specifically mentioned in this report.
This includes Basilea, Menarini Group, Shionogi and Wockhardt.
R&D Projects
This study includes five (5) case studies on the most promising projects
currently in the pipeline that, taken together, can save at least 160,000
lives from deadly, resistant bacterial and fungal infections each year. The
selected projects include: aztreonam-avibactam, cefepime-taniborbactam,
gepotidacin, olorofim and zoliflodacin. Note that after project selection, aztreonam-avibactam was approved by the European Commission on 22 April
2024. Four projects are in late-stage development (Phase II and onward)
as this is when companies are expected to start planning for access andstewardship. The selection was based on unmet medical need, AMR burden,
the World Health Organization’s Priority Pathogen Lists for bacteria andfungi (excluding Mycobacterium tuberculosis, due to different access andstewardship challenges, and national and supranational initiatives), and the
projects’ innovativeness** and capacity to overcome resistant pathogens.
Countries
The report’s geographical scope is global. However, for access planning,
the report focuses on 113 low- and middle-income countries (LMICs) where
greater access to medicine is needed, as defined in the geographic scope ofthe 2024 Access to Medicine Index Methodology.1*Innoviva Speciality Therapeutics and
Venatorx Pharmaceuticals are referred toas Innoviva and Venatorx respectively inthe rest of this report.

**As assessed by the four innovation criteria of the World Health Organization:
new chemical class, new target, newmode of action, and absence of known
cross-resistance.

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Access to Medicine Foundation

Executive summary
The development of replacement antibiotics that can treat rising drug-resistantinfections has fallen dangerously short. With a vast majority of large research-based
pharmaceutical companies no longer active in antimicrobial research and development (R&D) due to a lack of commercial viability, few new treatments that target
priority pathogens are making it to market – leaving people across the globe at risk.
Despite this reality, there are a handful of projects in late-stage clinical develop-

World Health Organization pipeline analysis
WHO pipeline
analysis reveals
howunder-isreveals
how underpreparedthepipelineprepared the pipeline isment that could help patients overcome some of the most severe drug-resistantinfections they are currently facing. The Access to Medicine Foundation has tracked
four such innovative, late-stage R&D projects across the pipelines of GSK, F2G,
Innoviva and Venatorx (gepotidacin, olorofim, zoliflodacin, and cefepime-tanibor-

12
antibiotics

bactam, respectively) as well as Pfizer’s recently approved aztreonam-avibactam(Emblaveo®).
Collectively, these projects could save at least 160,000 lives each year by pro-

Only 12 antibiotics
gained market approval
between 2017 and2021. Of these, only
2 represent a newchemical class.

viding much-needed medicines to treat drug-resistant gonorrhoea, urinary tract
infections (UTIs), intra-abdominal infections (IAIs), respiratory infections and invasive fungal infections. While these diseases and syndromes affect a wide rangeof patients globally, women and children – especially those living in low- and middle-income countries (LMICs) – are disproportionately affected.
To save as many lives as possible, it is vital to ensure these much-needed medicines reach the patients who need them most, particularly in countries that face
the highest burden of drug resistance. To achieve this, companies need to develop

5 projects analysed in this report could savecomprehensive access and stewardship plans during clinical development to makeat least 160,000 lives annually by providing

sure these drugs are made available and stay effective for as long as possible once
they make it to market.
What does this report find?  

medicines to treat drug-resistant gonorrhoea,
urinary tract infections, intra-abdominal infections, respiratory infections and invasive fungal
infections.

The five case studies reveal that companies are employing a diverse range of strategies within their access and stewardship plans, but structured advance planning has
not yet become standard, risking patient care globally. While all the companies are
conducting clinical trials in LMICs and have indicated some level of post-trial accesscommitments, these are not always detailed and clear. When it comes to stewardship planning, aside from some surveillance and data sharing strategies, overall
stewardship strategies are lacking across the board. Four key findings gleaned fromthe analysis highlight where efforts need to be scaled and how shortcomings can beaddressed.
1. Concrete plans for registration are lacking for almost all LMICs
For all five projects combined, concrete commitments for registration were identified for five LMICs – China, India, Mexico, South Africa and Thailand. However,for 108 of 113 LMICs in scope, where people also face high burdens of the diseases and syndromes targeted by these projects, it is currently unclear whether
any of them will be made available upon initial approval. Yet, to avoid lengthy registration procedures, the Global Antibiotic Research & Development Partnership(GARDP) plans to provide access to cefepime-taniborbactam (Venatorx) in 64
LMICs through export waivers and an international procurement agency.
2. Affordability and stewardship in LMICs are largely overlooked during planning
Some of the companies assessed in this report are addressing affordability andstewardship. For example, Pfizer applies specific pricing strategies for aztreonam-avibactam – and offers products in its portfolio at a not-for-profit basis
through its ‘Accord for a Healthier World’ initiative. However, no robust plans formaking new products affordable to patients in any LMIC could be identified in5Antimicrobial research & development

the other four case studies in this report. In addition, besides large companies,
like GSK and Pfizer who have comprehensive surveillance programmes in place,other strategies to ensure appropriate use – for example, by responsible promotion and ensuring supportive diagnostics – were lacking across the board.
3. Paediatric trials prior to market approval are a hopeful sign for children
Encouragingly, four of the five companies analysed – GSK, Pfizer, Innoviva and
Venatorx – are running or initiating clinical trials involving children. The efforts
from these four companies to prioritise children early on during clinical development are positive steps in moving towards closing the gap between adult andpaediatric access and set an example of what can be done by other developers.
4. Partnerships help scale efforts, but other tools to broaden access and stewardship plans are underutilised
Small- and medium-sized enterprises (SMEs) rely heavily on partners to help
commercialise products and drive global access. As demonstrated in this report,
partnering and collaborating with the publicly funded GARDP has enabled SMEs
to pursue access on a wider scale through licencing agreements that cover many
countries, including LMICs that face the highest burden of drug resistance. Asidefrom collaborations with GARDP, SMEs actively seek partnerships directly withlarge research-based pharmaceutical companies.
Over and above these vital partnerships and licensing agreements, companies– SMEs and large pharmaceutical companies alike – have opportunities to utilise
even more tools and strategies to advance their access and stewardship plans
more broadly. For example, to support companies in planning ahead for accessand stewardship, the Combating Antibiotic Resistant Bacteria Biopharmaceutical
Accelerator (CARB-X) – in collaboration with key partners, including the Wellcome
Trust and the Access to Medicine Foundation – published the Stewardship andAccess Plan (SAP) Development Guide in 2021. However, the report finds that thecompanies in scope are underutilising the recommendations in this Guide.
What’s next?
Both large research-based pharmaceutical companies and SMEs active in the antimicrobial R&D space need to pursue access and stewardship planning for all latestage clinical projects for antibiotics and antifungals, both innovative and adaptive.
For sustainable solutions to take hold, it is vital that comprehensive and detailed
access and stewardship plans are embedded in companies’ antimicrobial innovation,ahead of a product’s market approval. This includes, for example, targeting countries with particularly high burdens of disease and disproportionately affected populations, such as children, women and immuno-suppressed patients. To strengthen
their efforts and increase their reach, companies can seek out partnerships forco-development, as well as licencing agreements to ensure newly developed drugs
are made available to those who need them most.
With the SAP Guide being fit for purpose and signed off by multiple key stakeholders in the AMR space, companies have an opportunity to utilise it to help plan
effectively for access and stewardship – particularly by implementing its recommendations earlier in the development phase – without jeopardising the progress
towards market approval. At the same time, funders can also utilise the SAP Guide to
set contractual provisions on access and stewardship and hold companies accountable. In doing this, they can help ensure qualitative access and stewardship planningwill be implemented effectively throughout clinical development – while making suretheir vast financial support translates into sustainable progress and improved global
health. (For a comprehensive list of recommendations, see p.34 -35 of this report.)
It is critical to act now and make sure the few antimicrobials are made available
to patients on the frontlines of drug resistance.

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Access to Medicine Foundation

I NTRO DUCTI O NWhen the drugs don’t work
Antimicrobial resistance (AMR) is not a looming threat. Its unprecedented rise isedging the world closer to a reality where the medicines that revolutionised modern medicine will no longer work. Today, drug-resistant pathogens, or ‘superbugs’,
are spreading faster than predicted and patients across the world are battling
drug-resistant infections that cannot be treated with existing medicines. At thesame time, the development of new and innovative antibiotics and antifungals thattarget some of the world’s deadliest superbugs is failing to keep pace.
These drug-resistant bacteria and fungi can lead to a wide range of diseases andinfections and affect people across the globe in different ways. As illustrated in theaccompanying map, drug-resistant infections already claim the lives of people theworld over, but people living in sub-Saharan Africa (SSA) are hardest hit. For people living in this region, which is home to many low- and middle-income countries(LMICs), new and innovative treatments are critical. Without access to the rightantibiotics and antifungals, drug resistance will only develop further, spread wider
and cost more lives.

FIGURE 1 Drug resistance affects people globallyCentral and Eastern Europe and Cental

Drug-resistant pathogens know no borders and threaten the lives of people

Asia: At 31%, bloodstream infections

the world over. However, antimicrobial resistance (AMR) disproportionately

are the leading cause of deaths from

affects people in certain regions. Specifically in sub-Saharan Africa and Asia,

sepsis. However, the deadliest for chil-both regions that include many low- and middle-income countries (LMICs).

dren under the age five are lower-respiratory infections, mainly caused by
Streptococcus pneumoniae.

AMR Attributable Deaths
per 100k (2019)

Sub-Saharan Africa

23.7

South Asia

21.6

Central Europe, Eastern
Europe, and Central Asia

17.6

Latin America
and Caribbean

14.4

High-income

13

In South Asia, approximately
More than half of all AMR-related

2.37 million people died fromdeaths in children under the age of fivebacterial infections. More thanhalf of those can be associ-Southeast Asia,
East Asia, and Oceania

11.7

occur in sub-Saharan Africa. 561,000

North Africa
and Middle East

deaths can be associated and 129,000

ated with AMR, while around11.2

are directly attributable to AMR.

400,000 could be directly
attributed to AMR.

Source: IHME MICROBE database; data in the map is based on estimates from 2019.

7

Antimicrobial research & development

Who is most at risk?
Superbugs know no borders, putting the lives of people in countries across theglobe at risk. However, for people living in LMICs, where the burden of infectious
diseases is already higher, this risk is an everyday reality. Especially for the mostvulnerable, including infants and children, and for those living in countries facing thehighest threats of drug resistance. Oftentimes, patients in LMICs don’t have accessto newer treatments that are effective against drug-resistant pathogens, leaving
them vulnerable at best – or proving fatal at worst.
For children living in LMICs, already life-threating infections can prove fatal when
existing treatments are not effective or are unavailable.2 In these countries, forexample, bacterial resistance rates to gentamicin which – together with ampicillin –Neonatal sepsis in LMICs2,3

99% of all annual neonatal deaths
occur in LMICs

13% of these deaths are attributableto neonatal sepsis

680,000 babies lose their lives toneonatal sepsis

60% rate of resistance to gentamicin, a recommended

treatment for neonatal sepsis

is used to treat neonatal sepsis, is approximately 60%.3 This puts neonates (infants
under a month old) in LMICs, where 99% of global neonatal deaths occur, at evenmore risk.3
Drug resistance can also lead to childhood pneumonia becoming untreatable
and can lead to devastating outcomes, such as trouble breathing, bleeding into thelungs and even death from sepsis.4 Bacterial infections due to Streptococcus pneumoniae are the primary cause of pneumonia, although viruses and fungi can also
lead to pneumonia. In recent years, S. pneumoniae’s rate of resistance to penicillin,which is the recommended first-line treatment in many countries for children diag-

Pneumonia disproportionately
disproportionately affects
affects children
childrenPneumonia
under five
5 72
under
Childhood pneumonia killed over 740,000
children in 2019

nosed with severe pneumonia, has increased to over 60%. For example, in Vietnam
resistance rates of 99% were found.5
These examples are only snapshots of the harsh impact drug-resistant infections
have on people living in LMICs. Drug-resistant pathogens affect lives through a far
wider range of syndromes and infections as well (also see fact sheet on p.11 of this2 in 3 children with pneumonia do not receive
the antibiotics they needreport). Aside from the fatal drug-resistant infections that are rising, some of thelife-changing medical procedures that have been made possible with the availabilityof effective antibiotics are also under threat. Many of the dangerous pathogens thatcan cause drug-resistant infections are present in hospital settings, putting alreadyvulnerable patients, and those who need to undergo standard medical procedures

Cancer patients are at high risk
Cancer patients are at high risk6

at risk.

Bacterial infections are the 2nd leading

Oncology treatments, caesarean-sections and hip replacements, for example,

cause of death amongst cancer patientsare only possible if effective antibiotics are on hand to prevent infection. Cancer
patients, who undergo therapies that can be aggressive and compromise theirimmune systems, are particularly susceptible to contracting bacterial infections.
In fact, bacterial infections are the second most prevalent cause of death amongcancer patients and result in the hospitalisation of 1 in every 5 patients undergoingtreatment.6 Historically antimicrobials have been effective in supporting patients

1 in 5 patients undergoingtreatment will be
hospitalised as a result

undergoing oncology treatment. However, clinicians are increasingly observing
infections that are resistant to previously effective antibiotics that could treat themand cure the infection.
Only a handful of companies are targeting the deadliest pathogens
In response to the threat posed by some of the most dangerous, drug-resistantsuperbugs, the World Health Organization (WHO) published its first-ever bacterial Priority Pathogen List in 2017, followed by the second iteration in 2024.
Furthermore, the WHO published its fungal Priority Pathogen List in 2022. In a
bid to guide and promote R&D of innovative antimicrobials, these lists provide aclear call to action for pharmaceutical companies, indicating where to focus theirresources and efforts (also see sidebar on p.9).

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Access to Medicine Foundation

What is an innovative antimicrobial?
In 2024, the World Health Organization (WHO) published the second iteration of the WHO
bacterial Priority Pathogens List (WHO BPPL), summarising 14 pathogens, in addition to
Mycobacterium tuberculosis, that have the greatest potential to harm human health.7 Inspired by
the proven value of the WHO BPPL, the WHO published the first WHO fungal Priority Pathogens
List (WHO FPPL) in 2022. The WHO FPPL outlines 19 fungi recognised as posing the greatest
threat.8
The pathogens listed in the WHP BPPL and the WHO FPPL are categorised into three
distinct groups, aligning with the urgency for development of new antibiotics and antifungals to
address them: critical, high and medium priority.
In 2021, the WHO conducted an analysis of all the antibacterial agents in clinical andpreclinical development. In addition, the WHO identified whether the agents in development
were innovative using the WHO innovation criteria. This report employs the WHO innovation
criteria, meaning that for an R&D project to be considered innovative, it must fulfil at least oneof the four predefined criteria for innovation, namely: the absence of known cross-resistance, a
new target, a new mode of action (MoA), and/or new chemical class. For the fungal projects noassessment is made on their innovativeness as this data is not readily available.
In addition to the WHO BPPL and the WHO FPPL, the WHO Paediatric Drug Optimisation for
Antibiotics (WHO PADO) list highlights important products for which optimal formulations for
paediatric populations are needed.9 Without optimal treatments being made available for children,
healthcare providers and parents often resort to using or manipulating adult medicine, increasing
the risk of inadequate dosing and spurring drug resistance.9 However, it must be noted that developing paediatric formulations is challenging; it requires ensuring maximal efficacy and no toxicity,while simultaneously being easy to administer. Additionally, before recruiting children for clinical
trials, there are stricter ethical considerations that need to be addressed.

The clinical pipeline for antimicrobial medicines has struggled to keep pace withrising drug resistance (see figure alongside). In recent years more and more large
research-based pharmaceutical companies have abandoned antimicrobial R&D

World Health Organization pipeline analysis
WHO pipeline
analysis reveals
howunder-is73
reveals
how underpreparedthepipelineprepared the pipeline isand commercialisation, with recent decisions by AstraZeneca, Bayer, Bristol-Myers
Squibb, Eli Lilly, Johnson & Johnson, Novartis and Sanofi to leave, or significantly
minimise their presence in this space. Given this reality, the world has come to relyon small- and medium-sized enterprises (SMEs) to plug the gap. However, these‘biotechs’ lack the vast financial resources that large pharmaceutical companies
have, leading to many going bankrupt.
Of course, several pharmaceutical companies invest in the AMR Action Fund that

12
antibiotics

Only 12 antibiotics
gained market approval
between 2017 and2021. Of these, only
2 represent a newchemical class.

works to develop new antimicrobials, and R&D funder organisations – public andprivate – currently invest in or provide grants to companies for the development of
new antimicrobials. However, this is not sufficiently addressing the lack of access toantimicrobials, nor is it enough to build up the antimicrobial R&D pipeline.
Given the current R&D landscape, how can lives be saved today?
People across the world urgently need access to innovative antimicrobials, which is
why it is vital to engage in long-term, sustainable efforts to ensure that, at the very
least, the few promising drugs in development reach patients that need them most.
Specifically, companies need to develop and implement access and stewardshipplanning as early as possible in the R&D process that is designed to address priority
populations’ access requirements, regardless of geography.
To date, the Access to Medicine Foundation’s AMR Programme has found thataccess strategies for antimicrobial products already approved, and on the market,
have not been implemented at scale. The 2021 AMR Benchmark, for example, foundthat just one third of antimicrobial products in the portfolios of companies in scope
are covered by access strategies in LMICs.10 This emphasises the need for advanceplanning of access and stewardship plans for projects that are still in development.
The five case studies in this report zero in on the access and stewardship planning of R&D projects of two large research-based pharmaceutical companies (GSKand Pfizer) and three SMEs (F2G, Innoviva and Venatorx), specifically to determine
whether plans are targeting the LMICs that are facing the greatest threats.

9Antimicrobial research & development

Should these projects prove safe and effective and successfully leave the R&D
pipeline, the resulting new antimicrobial products will have a significant impact on
the lives of patients battling drug-resistant infections. As set out in the accompanying fact sheet on p.11, these projects target a wide range of diseases and syndromes,
including drug-resistant gonorrhoea, urinary tract infections (UTIs), intra-abdominal
infections (IAIs), respiratory infections and invasive fungal infections. By providing
patients with much-needed medicines to treat these diseases and syndromes, thelives of at least 160,000 people could already be saved each year.*
While findings from this report show that advance access and stewardshipplanning has not become the norm yet, there are clear opportunities for industry
to enhance efforts, address gaps and drive stepwise change to ensure patients arereached. Moreover, many of the projects analysed are being developed with thesupport of partner funding, and these organisations can help ensure companies willdevelop – and follow up on – access and stewardship plans. By doing this, they canensure their vast financial support for antimicrobial R&D translates into sustainable
progress and improved global health.

*This number is based on the number of deaths per syndrome annually due to the resistant pathogens that are specifically targeted by the projects in scope. The data is derived
from the estimated global burden of bacterial antimicrobial resistance in 2019 by theInstitute for Health Metrics and Evaluation.11 Note that the number of deaths due to invasive aspergillosis caused by drug resistant Aspergillosis spp. is not estimated and therefore not included.

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Access to Medicine Foundation

A CLOSE R LOO K
The global impact of the diseases targetedby the projects analysed in this report.

R ES PI R ATO RY
I N FEC TI O N S

U R I NARY TR AC TI N FEC TI O N S (UTI s)

Most caused by

Most caused by E. coli

S. pneumoniae andS. aureus

413,000

GONORRHOEA
Caused by N. gonorrhoeae
Gonorrhoea, a sexually

375,000transmitted infection (STI),
is a major public healthpeople died in 2019 glob-

threat globally.

ally, as a result of UTIs.11

estimated deaths in 2019,
infections the leading
cause of AMR-related

50-60% of women will

deaths.11

develop at least one UTII NVA S IVE FU N GALI N FEC TI O N S

Most caused by E. coli

For example, caused

and S. aureus

by A. fumigatus

1,281,000

Fungal diseases dis-caused by complicatedimmunocompromised anddeaths globally were

82.4 million

making lower respiratory

AB D O M I NALI N FEC TI O N S

intra-abdominal infections

estimated new cases(cIAIs) in 2019. 63% ofworldwide in 2020.

those were associated18

hospital are increasingly
associated with multidrug
resistance and result inpoor clinical outcomes andhigher mortality rates.12>50% of women haveasymptomatic infections,preventing them fromthe appropriate treatment.

Each year26

Women are specificallytive treatment options,

7 million

affected with complicated

due to drug resistance,

people are affected by

infections and worse

make IAIs hard to treat inlife-threatening fungal

outcomes.19 Gonorrhoea

LMICs.

diseases.

2.5 million
people die as a direct cause

transmission.20
Children in Western
sub-Saharan Africa facea high prevalence ofWithout treatment
options, community-­acquired pneumonia is themost common cause of
sepsis and a major causeof hospitalisation anddeath.13
IN THE NEWS>92% of the bacteria thatcause UTIs are resistant
to at least one common

N. gonorrhoeae has

cIAIs.22,23 Children underdeveloped resistance tothe age of five, and men,

all antibiotics, including

are specifically affected.

antibiotic.16

ceftriaxone, the lastavailable recommended

With increasing resistanceIf complicated UTIs cannot

treatment option. Cases ofrates, usually treatablesuch ‘Super-Gonorrhoea’

infections are more often

are emerging globally.20

turning into deathly cIAIs.

be treated, they can leadto sepsis and even septic
shock.15
IN THE NEWSIf untreated, cIAIs can lead
If untreated, or whento systematic complica-

untreatable, gonorrhoea

tions, such as sepsis.24

can cause serious, lifelong
consequences, such as“Undiagnosed
pneumonia outbreakin China puts pressure
on pediatric hospitals,

IN THE NEWSinfertility and arthritis.19“Urinary Tract Infection
affect millions. The

and cancer patients, andInaccessible and ineffec-

increased risk of HIVprocedures and getting

as those in ICUs, COPD
people living with HIV.

can lead to a five-foldparticipating in screening

vulnerable patients, suchwith AMR.11

within their adult lives.15

Infections acquired in the

proportionately affectcures are faltering.”17

1 million
COPD patients die due toinvasive aspergillosis.

Emerging rates of resistance are threatening theeffectiveness of azoles– the current treatment
option for aspergillosis. If
untreated, death rates forinvasive aspergillosis go up
to >95%.26>10% azole resistancefound in A. fumigatus
samples globally.27

IN THE NEWS“How E. coli infections

prompts questions” 14of the fungal disease.

IN THE NEWSwreak havoc on the“Super-gonorrhoea’s
spread causing hugeconcern”21

body, causing dangerous disease – particularly in kids”25“Global deaths fromfungal disease havedoubled in a decade –new study” 28

AT LE AST 160,000 LIVES
could already be saved from deadly drug-resistant infections
each year if patients around the world were able to access thefew ­promising antimicrobials assessed in this report.

11

Antimicrobial research & development

ACCESS AN D STEWARDSH I P DU RI NG R&D

From pipelines to patients
Using the priority pathogens for R&D of new antibiotics and antifungals listed by
the World Health Organization (WHO) (also see p.9), the Foundation has scoped
promising late-stage R&D projects that are currently in the pipeline. The WHO
updates these priority lists to accurately represent gaps in the pipeline and global
unmet needs. Companies can consistently refer to them when making strategic
decisions about their antibacterial and antifungal pipelines in the future.
What is currently in development to target superbugs?
Ideally, to be adequately prepared and keep pace with the sheer speed at which
drug resistance is developing, there should be an abundance of late-stage R&D projects targeting a wide range of the WHO’s listed priority pathogens.
Currently there are only 19 antibacterials in late-stage development targeting 8priority pathogens (see Figure 2 on p.13). Notably, there is not a single project in theclinical pipeline (early, or late stage) addressing the other 6 of the 14 bacteria designated as priority pathogens by WHO. This leaves infections caused by Enterococcus
faecium, Group A Streptococci, Group B Streptococci, Non-typhoidal Salmonella,
Salmonella Typhi, and Shigella spp. completely unaddressed. Three of which, Nontyphoidal Salmonella, Salmonella Typhi, and Shigella spp., cause diarrhoeal disease,which is the third leading cause of death in children under five years of age.29 E.
faecium can cause a variety of infections, including urinary tract infections (UTIs) as
well as intra-abdominal infections (IAIs).30
Similarly, there are currently only 7 antifungals in late-stage development targeting 18 priority pathogens (see Figure 3 on p.14). Although there are very few
antifungals in late-stage development, most of them act against a wide range ofpathogens, which leaves only one priority pathogen – Talaromyces marneffei –entirely unaddressed. Inhaling Talaromyces marneffei spores may lead to the onsetof Talaromycosis, an infection primarily observed in immunocompromised people,
including cancer patients and people living with HIV.31
Narrowing in on four bacterial pathogen projects and one fungal pathogen
project
Of the limited projects currently in late-stage development across both the antibiotic and antifungal pipelines, this report analyses five promising projects for individual, in-depth case studies. During the period of analysis, one of these projects, aztreonam-avibactam, was approved by the European Commission (22 April 2024). Of
the five featured projects, four are antibiotic agents and one is an antifungal agent.
The projects were selected based on WHO innovation criteria, priority pathogens, unmet medical need, and high resistance rates to current treatments.
Furthermore, the projects were selected to reflect a balance of large researchbased pharmaceutical companies and small- and medium-sized enterprises (SMEs),
with more of the featured projects belonging to SMEs, reflective of the current
antibacterial and antifungal R&D landscape.
Three of the four selected antibacterial agents also meet at least one of fourinnovation criteria outlined by WHO. Specifically, cefepime-taniborbactam, gepotidacin and zoliflodacin all fulfil the new chemical class criterion making them potentially very impactful projects. While the fourth remaining antibacterial agent aztreonam-avibactam does not meet any of the WHO innovation criteria, it is highlighted
as a noteworthy pipeline agent by the WHO and highlighted in WHO’s PaediatricDrug Optimisation for Antibiotics (WHO PADO) list as a compound that may be of12

Access to Medicine Foundation

FIGURE 2 Late-stage R&D projects targeting bacterial pathogens
This figure shows the 14 priority pathogens recognised by the World HealthOrganization bacterial Priority Pathogen List (WHO BPPL) 2024 for theurgency in development of new antibiotics.7 The burden attributable to theresistant strains of bacteria outlined in the WHO BPPL is summarised by the
number of deaths per year globally.11 The right side of the figure details all
late-stage R&D projects currently progressing within the pipelines of bothlarge research-based pharmaceutical companies and small- and medium-sized enterprises (SMEs), specifically directed towards combating thesepriority pathogens.
Deaths attributable to resistant

Pipeline Projects

pathogen strains

Phase IIc

Acinetobacter baumannii (CR)

Phase IIIf*

Enterobacterales (3GCR)Enterobacterales (CR)

g

r

o

p

d

g

h

d

g

r

h

s

i

j

k

r

Salmonella Typhi (FQR)
Shigella species (FQR)
Enterococcus faecium (VR)Pseudomonas aeruginosa (CR)
Non-typhoidal Salmonella (FQR)
Neisseria gonorrhoeae (3GCR and/or FQR)
aStaphylococcus aureus (MR)

b

f

m

q

e

Group A Streptococci (MacR)
Streptococcus pneumoniae (MacR)l

Haemophilus influenzae (AmpR)nnGroup B Streptococci (PenR)
Not estimated

0

50k

100k
● WHO innovation criteria fulfilled● WHO innovation criteria not fulfilled● Innovativeness not assessed by WHO
a. Afabicin (Debiopharm), b. Brilacidin (Innovation Pharmaceuticals),c. BV100 (BioVersys), d. Cefepime + taniborbactam (GARDP and Venatorx
Pharmaceuticals), e. Cefilavancin (R-Pharm and Theravance Biopharma),f. Finafloxacin (MerLion Pharma), g. Funobactam + imipenem + cilastatin(Evopoint Bioscience), h. Gepotidacin (GSK), i. Nacubactam + aztreonam (Meiji
Seika), j. Nacubactam + cefepime (Meiji Seika), k. Nacubactam + meropenem(Meiji Seika), l. Nafithromycin (Wockhardt), m. Nilofabicin (CrystalGenomics),
n. Solithromycin (Fujifilm Toyama Chemical), o. Sulopenem; sulopenem etzadroxil / probenecid (Iterum Therapeutics), p. Tebipenem pivoxil (GSK),
q. TNP-2092 (TenNor Therapeutics), r. Zidebactam + cefepime (Wockhardt),
s. Zoliflodacin (GARDP and Innoviva)
Note: During the period of this report’s analysis, one of the projects in scope,aztreonam + avibactam (AbbVie and Pfizer) was approved by the European
Commission (22 April 2024). As such, the project is not reflected in this pipeline figure.

*includes resistance data against
fourth-generation cephalosporin forEnterobacter spp.

13

Antimicrobial research & development

FIGURE 3 Late-stage R&D projects targetingcritical fungal pathogens
This figure lists the 19 priority pathogens

Pipeline Projects

recognised by the World Health Organization

Phase IIfungal Priority Pathogen List (WHO FPPL) 2022,
listed by priority for the urgency in developmentof new antifungals.8 Unlike in Figure 2, thePhase III
b

c

c

d

e

f

Candida auris

b

c

d

g

Candida albicans

b

c

d

g

Candida glabrata

b

c

d

g

Candida tropicalis

b

c

d

g

Candida parapsilosis

b

c

d

g

Histoplasma speciesdMucoralesc

Cryptococcus neoformans
Aspergillus fumigatusag

attributable deaths associated with these priority
pathogens have not been illustrated as such data
is underreported. In addition, the innovativenessof these R&D projects has not been assessed byWHO. The figure details all late-stage R&D
projects currently progressing within thepipelines of both large research-based pharmaceutical companies and small- and medium-sizedcompanies (SMEs), specifically directed towards
combating these priority pathogens.

Eumycetoma causative agentseccFusarium species
Scedosporium speciesecLomentospora prolificansecCoccidioides species

e

c

d

Cryptococcus gattibcCandida kruseicdPneumocystis jirovecii

dgParacoccioides speciesdgTalaromyces marneffei● Innovativeness not assessed by WHO
a. BAL2062 (Basilea), b. Encochleated ampothericin B(Matinas BioPharma Holdings, Inc.), c. Fosmanogepix(Basilea), d. Ibrexafungerp (Scynexis), e. Olorofim (F2G),
f. Opelconazole (Pulmocide), g. Rezafungin (Mundipharma)

14

Access to Medicine Foundation

How access and stewardship planning can ensure patients are reached

Strategies companies can consider when

The analysis of case studies that follows determines the depth and breadth ofdeveloping effective access and stewardship

access and stewardship planning that companies are currently implementing.
Specifically, having already set out where their products would be needed the most,the analysis identifies whether companies are targeting the low- and middle-income countries (LMICs) that are facing the highest threats. If lives are to be saved,
it is crucial that the regions currently disproportionately affected by the targeted
pathogens are prioritised to receive appropriate access to newly developed products that may result from the projects in the pipeline.
Companies have diverse tools for ensuring access and stewardship (see box-out
alongside), and it is not necessary for every company to apply every available strategy to its access and stewardship plan. Appropriate access and stewardship strategies will also vary, depending on the product at hand, and its specific characteristics.

plans▶ Access• Registration• Collaborative registration or availability
mechanisms (e.g., EU-M4all, special
importation waivers, WHO Collaborative
Registration Procedure, WHO
Prequalification)• Responsible intellectual property andlicensing agreements• Early access programmes• Manufacturing and supply• Equitable pricing• Clinical trials in LMICs and post-trial access

Taking proactive steps early in the development process

commitments

Certain components of access and stewardship plans can already be undertaken• Paediatric formulations

earlier in clinical development, while others may take shape later in the develop-• Product donation programmes

ment process. However, it is critical for all companies to consider, as early in thedevelopment process as possible, which populations could benefit from this project
if it eventually reaches the market. By doing so, companies proactively identify target populations and gain a better understanding of the countries with the highest▶ Stewardship• Surveillance and data sharing• Responsible promotion and sales strategies• Availability of supportive diagnostics

disease burden, as well as the distinct characteristics within the target population –such as whether paediatric populations are disproportionately affected. For example, obtaining market approval for paediatric use typically takes up to ten years
longer than adult use.32 Therefore, having a paediatric formulation under development before market approval of the adult formulation will drive progress towards
closing the gap between adult and paediatric access.
Identifying these factors early on allows companies to take them into consideration during the development process. This is crucial because countries may havespecific regulatory requirements for approval, that companies may not foresee in atimely manner.
For instance, some countries may require an in-country clinical trial, which, if notplanned for, can significantly impact the waiting time for patients to access a product. Therefore, it is encouraging when companies already have a preliminary list of
countries where they plan to prioritise filing for registration, particularly when thesedecisions are informed by data on the burden of disease. This indicates that thecompany has already considered which populations could benefit from the project.

How appropriate and timely access toinnovative antibiotics can save people’s lives
from resistant infections
Early access programmes provide patientswith a pathway to access medicines that are
yet to be registered in a country and can beparticularly impactful for patients who haveexhausted all existing treatment options.
For example, in August 2022, a 50-year-old
woman from Nepal was infected with multidrug-resistant P. aeruginosa after undergoing
abdominal surgery. The intra-abdominal
infection caused by the pathogen induced

Using the Stewardship and Access Plan Development Guide

sepsis, leaving the patient in critical condition.

When developing an access and stewardship plan, companies can utilise the
Stewardship and Access Plan (SAP) Development Guide, published in 2021 by the
Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X)
in collaboration with key partners, including the Wellcome Trust and the Access to
Medicine Foundation.34 The Guide provides practical guidance that companies canuse to inform and scale up their access and stewardship plans. It was specificallydesigned to assist SMEs, particularly CARB-X awardees, in developing appropriate
access and stewardship plans while also serving as a template for other productdevelopers in the global health community. While the SAP Guide offers practical steps
for companies in access and stewardship planning, its relevance may vary for eachcompany, and some companies report implementing plans independent of the SAP
Guide. However, it is critical that the depth and breadth of companies’ access andstewardship plans are in line with the recommendations set out in the SAP Guide. In
addition, the Access to Medicine Foundation has been assessing pharmaceutical com-

As existing antibiotics (ceftazidime/avibactam, imipenem/relebactam and ceftolozane/
tazobactam) could not cure the infection, aPhase III antibiotic (cefepime/zidebactam)
developed by Wockhardt was provided underan early access programme. In receiving thisinnovative antibiotic, the patient was cured
from an otherwise untreatable infection, andshe left the hospital in a stable condition.33
While this example illustrates how an early
access programme can help provide timely
access to innovative medicines that are notyet registered, this strategy is only one ofmany components that can be utilised bycompanies as part of developing comprehensive access plans.

panies approaches to appropriate access and stewardship since the publication of thefirst AMR Benchmark in 2018, setting clear expectations on how companies can act.

*The Guide was developed collaboratively by a working group comprising of
CARB-X, several of its funders, which
include the United States Department
of Health and Human Services’ (HHS’)

Office of Global Affairs (OGA) andBiomedical Advanced Research andDevelopment Authority (BARDA); theGlobal AMR Innovation Fund (GAMRIF);UK Department of Health and Social

Care (DHSC); the Bill & Melinda Gates
Foundation and the Wellcome Trust, as
well as the Global Antibiotic Research andDevelopment Partnership (GARDP) andthe Access to Medicine Foundation, with

consultative input from the Biotechnology
15
Innovation Organization (BIO).

Antimicrobial research & development

ANALYIS: CO M PANY CASE STU D I ES

Assessing the five selected projects
This report focuses on the five projects from F2G, GSK, Innoviva, Pfizer and
Venatorx, highlighting which elements of their current access and stewardshipplanning are on track – and identifying what needs to be done to ensure they
address gaps in these plans. Findings from the case studies can also provide othercompanies with guidance on what to focus on to ensure they take proactive andpre-emptive action to implement effective access and stewardship planning.
The table below provides an overview of the access and stewardship planning forthe projects analysed, with the individual case studies taking an in-depth look at thevarious strategies that are being employed.
Following the case study analyses, the report also considers how R&D funderorganisations – private or public organisations that invest in or provide grants tocompanies for the development of new antimicrobials – can work with companies
to make progress.
Note: Throughout the case studies, several abbreviations are used. Please refer top.36 -37 in this report for a list of abbreviations for reference.

FIGURE 4 Companies apply diverse range of strategies within access and stewardship plans
The table shows to what extent the five companies are incorporating various strategies in their accessand stewardship and plans.** The most appropriate strategies depend on the project and company inquestion – not all strategies are apprioriate for all projects and companies.

Product

Strategy not in place or no

GSK

PfizerVenatorx

Innoviva

F2G

Gepotidacin

Aztreonam-

Cefepime-

Zoliflodacin

Olorofim

avibactam

taniborbactam

uUTI,

cIAI, HABP/

cUTI, HABP/

Gonorrhoea

Invasive fungal

gonorrhoea

VABP, cUTI,

VABP

information available
Strategy partially in place for LMICs

TargetStrategy in place for LMICs

indication

infections,

infections due

includingto aerobic

invasivegram-negative

aspergillosis

organisms
AccessRegistration
Responsible intellectual property and licensing agreements
Early access programmes
Manufacturing and supply
Equitable pricing
Clinical trials in LMICs and post-trial access commitments
Paediatric formulations
Collaborative registration or availability mechanisms*
Product donation programmes
Stewardship
Surveillance and data sharing
Responsible promotion and sales strategies
Availability of supportive diagnostics*These include mechanisms such as
EU-M4all, special importation waivers, WHO Collaborative Registration
Procedure and WHO Prequalification**For a strategy to be in place, the company reports a clear, well-described, anddetailed plan, either at product level or ona wider scale specifying the geographic
reach for the 113 LMICs in scope. A strat-

egy that is partially in place has limited
information on how the company’s planaddresses access or stewardship for the
113 LMICs in scope.

16

Access to Medicine FoundationC A SE S T U DY 1

Plans for gepotidacin to fulfil global needs of patients
yet to mature
Gepotidacin, which belongs to a new chemical class of antibiotics and has a newmode of action, is currently being developed by GSK to treat patients with uncomplicated urinary tract infections (uUTIs) and uncomplicated urogenital gonorrhoea.
Half of all women develop at least one urinary tract infection (UTI) during their

Product
Gepotidacin
Target pathogen(s)adult life, and resistance rates of UTI-causing Escherichia coli infections are rising.

16

Similarly, as experts warn that gonorrhoea is increasingly becoming resistant to all
available antibiotics, global access to new antibiotics, such as gepotidacin, is crucial
to alleviate the burden of gonorrhoea.
GSK seeks market approval for two indications
GSK plans to submit a New Drug Application (NDA) for uUTI in the second half of• N. gonorrhoeae (third-generation
cephalosporin-resistant and/or
fluoroquinolone-resistant)• Enterobacterales (Carbapenem-resistant
E. coli); E. coli (ESBL producing)Target indication(s)uUTI, gonorrhoea

2024, followed by the submission for gonorrhoea in 2025, both to the US Food andMode of administration

Drug Administration (FDA).37

Oral

Despite positive Phase III trial results for gepotidacin in treating uUTIs in April
2023, GSK pushed back the deadline to file for registration from June 2023 to thesecond half of 2024.38 While the reason for this shift remains unclear, it will inevitably result in a delay in access to gepotidacin globally.38 In addition, there is currently
no early access plan in place for gepotidacin, which would make it available aheadof market approval.
Populations with medical need, including children, prioritised in clinical trials
To address needs in low- and middle-income countries (LMICs) with a high burdenof disease, GSK is conducting clinical trials in such countries. For example, its Phase
III clinical trial for uUTIs was conducted in India where the most deaths due to carbapenem-resistant E. coli occur – with E. coli being the single most common causative pathogen for uUTIs.39
In addition to the adult formulation for women, there is a paediatric oral formulation of gepotidacin currently under development in Phase I of clinical trials. These
trials include paediatric patients aged 2 – 12 and aim to address the unmet medical
need of uUTIs in paediatric populations.40 This could lead to the acceleration ofaccess to gepotidacin for children.

Phase• Adult formulation for uUTIs: Phase III(completed)• Adult formulation for gonorrhoea: Phase
III (completed)• Paediatric formulation for uUTIs: Phase I(completed)
Clinical trials in LMICs in scope• uUTIs: Mexico and India• Gonorrhoea: Mexico
Funding partners
BARDA reports it
has provided USD
203.8 million since
2013.

35

No contractual
provisions onaccess and stewardship planning

Defense Threat
Reduction
Agency36

reported as partof these funding
announcements

Structured plans to make gepotidacin widely accessible and affordable in
LMICs not yet in place
Limited information is available on how gepotidacin will reach patients in LMICs in
scope of this report. For example, it is unclear in which LMICs GSK plans to register
gepotidacin upon initial approval. However, GSK reports that is seeking to bringgepotidacin to patients globally for the treatment of gonorrhoea and uUTIs, whereunmet need exists. In addition, GSK publicly reports it only conducts clinical trials
in countries where it also intends to file for registration.41 Given that GSK is undertaking clinical trials in Mexico and India, filing for registration of gepotidacin can be
expected in Mexico for treatment of uUTIs and in India and Mexico for the treatment of gonorrhoea. Furthermore, GSK does not file patents, nor does it enforce
historic patents, for its medicines in least-developed countries and low-income
countries, which enables generic manufacturers to also supply to these countries.
For gonorrhoea, GSK reports that it will closely monitor the development of
Innoviva’s zoliflodacin, an alternative second-line treatment for gonorrhoea currently in late-stage development, and assess the potential of these two new antibiotics in the global management of multidrug-resistant gonorrhoea.

17Antimicrobial research & development

Although GSK generally reports employing responsible pricing strategies in LMICs
to expand product reach and ensure affordability, it remains unclear which exact
pricing strategies will apply to gepotidacin and whether patients’ ability to pay will
be considered.
Commitment to surveillance for appropriate use and education support
GSK reports that introduction of gepotidacin in LMICs would be accompanied byeducational programmes on the risks of AMR, which will include resistance surveillance.42 Specifically for gepotidacin, GSK initiated a uUTI Global Surveillance Studyin 2019. The study consisted of surveilling data from 73 medical facilities across the
US, Europe, the Asia-Pacific region, and Latin America.43 GSK is also collaboratingwith Amref Health Africa to drive collaboration between local actors in supporting
the implementation of AMR plans, including surveillance.42
Unclear to what extent GSK will pursue global access for gepotidacin
GSK has exclusive market rights in all 113 LMICs in scope of this report, where
better access to medicine is urgently needed, including gepotidacin. Despite thispotential for providing access in these countries, to both adult and paediatric populations, it is currently unclear what the delivery of gepotidacin will look like in these
113 LMICs after the product’s global launch. Aside from a paediatric formulation inearly-stage development, clinical trials in at least two LMICs (India and Mexico), andstewardship commitments, specific details on access plans for gepotidacin, such as
registration filing and equitable pricing strategies, are lacking.

FIGURE 5 Gepotidacin has the potential to impact lives globally
The map indicates the countries that have the highest burden attributableto carbapenem-resistant Escherichia coli and fluoroquinolone-resistant
Neisserria gonorrhoea, measured by disability adjusted life years (DALYs).*
While the burden of fluoroquinolone-resistant N. gonorrhoea is widespread
globally, the burden of carbapenem-resistant E. coli is particularly prevalent
in South Asia, and parts of North-West Africa.

At 39%, India has the highest rate of carbapenemresistant E. coli, which can cause uUTIs andother infections. In 2019, it was estimated thatover 16,000 people in the country died due tocarbapenem-resistant E. coli.

GSK HQ● High burden of carbapenemresistant N. gonorrhoea● High burden of carbapenemresistant E. coli
● High burden of carbapenemresistant E. coli and carbapenemresistant N. gonorrhoea■ Clinical trials present in LMICs*A threshold of 0.95 DALYs per 100,000
people was used to determine countries
with a high burden of fluroquinolone-resistant N. Gonorrhoea. DALYs were chosen as the unit of measurement because

while mortality is low (0.5% to 3% of
untreated infections) gonorrhoea cancause serious, lifelong consequences inmen and women. To determine countries
with a high burden of carbapenem-resist-ant E. coli a threshold of 27 DALYs wasused. Please note that, due to the scaleof the map, some countries with high burden of disease or resistance might not
be visible.

Source: Burden of pathogens: IHMEMICROBE database, Trial locations: NIH
Clinical Trials

18

Access to Medicine FoundationC A SE S T U DY 2

Despite varied plans, it is uncertain how recently approved
aztreonam-avibactam will reach LMICs
Aztreonam-avibactam (ATM-AVI) was jointly developed by Pfizer and AbbVie,
whereby AbbVie holds the commercialisation rights for the US and Canada, andPfizer for the rest of the world.46 While this product is a combination of two existing
antibiotics, its clinical utility is significant due to its effectiveness against a variety of infections caused by multidrug-resistant gram-negative bacteria, includingEnterobacterales, which are a main cause of respiratory and intra-abdominal infections.46 This could make ATM-AVI a viable last-resort treatment option for patientswith limited or no existing treatment options due to drug resistance and, therefore,
address unmet medical need in this patient population.
Building on the positive Phase III trial results in 2023, Pfizer filed for registration in Europe in September of the same year.47 On 22 April 2024, the European

Product
Aztreonam-avibactam (Emblaveo®)
Target pathogen(s)Multidrug-resistant Enterobacterales (including MBL producing), Stenotrophomonas
maltophilia
Target indication(s)cIAI, HABP/VABP, cUTI (including
pyelonephritis), infections due to aerobic
gram-negative organisms
Mode of administration

Commission approved ATM-AVI for the treatment of adult patients with compli-IVcated intra-abdominal infections (cIAI); hospital-acquired bacterial pneumonia

Phase(HABP), including ventilator-associated bacterial pneumonia (VABP); complicatedurinary tract infections (cUTI), including pyelonephritis; and other infections due to
aerobic gram-negative organisms in patients with limited treatment options.48 In
addition, Pfizer is planning regulatory filings in the UK and China.46 While no early
access programme is yet in place, Pfizer reports it is pursuing such programmes in
multiple countries to meet patient needs.
Equitable pricing plans in place to increase affordability
Pfizer reports it will implement equitable pricing strategies for ATM-AVI. For example, pricing will be based on burden of disease data, including the local epidemiology and patient population characteristics, as well as data relating to the affordability of ATM-AVI, such as national reimbursement, potential out-of-pocket costs,
gross domestic product (GDP) per capita data and healthcare benefits. In line with
its internal policy, Pfizer will not file and/or enforce patents for ATM-AVI in least-developed countries (LDCs).42
In addition, ATM-AVI will be evaluated for Pfizer’s ‘Accord for a Healthier World’initiative. Through this initiative, Pfizer offers its full portfolio of medicines andvaccines, for which it holds global rights, on a not-for-profit basis to 45 LMICs.49
The Accord covers most countries in sub-Saharan Africa (SSA), where the burden of respiratory and intra-abdominal infections due to multi-drug resistantEnterobacterales is especially high (see map on next page).11 If ATM-AVI will fall

• Adult formulation: approved April 2024
• Paediatric formulation: Phase II (ongoing)
Clinical trials in LMICs in scope
Phase III: China, India, Mexico, Philippines,
Thailand, and Ukraine
Phase II (paediatric): China and India
Funding partners
2015: BARDA
reports it, since2015, has provided
Pfizer with USD 96
million to develop
ATM-AVI.

44

2015: European
Union’s IMI invests
EUR 83 million
through the project

No contractual
provisions onaccess and stewardship planning
reported as partof these funding
announcements

COMBACTE-CARE(this includes, but
is not specific to,
ATM-AVI).45

under the Accord, affordability in 45 LMICs could be enhanced.
Pfizer addresses unmet medical need of children
In children under the age of five, carbapenems – currently the last-resort antibiotics – are already ineffective in 19% of all bacterial infections.50 As such, ATM-AVI
is included in the World Health Organization Paediatric Drug Optimisation for
Antibiotics (WHO PADO) list, which highlights pipeline projects and products thatare urgently needed for paediatric populations.32 While an adult formulation of
ATM-AVI was recently approved, Pfizer aims to accelerate access to ATM-AVI forchildren by developing paediatric formulations in parallel. For example, Phase II trials for ATM-AVI are ongoing in children between the ages of 9 months and 17 years.

19

Antimicrobial research & development

ATM-AVI included in Pfizer’s portfolio-wide antimicrobial stewardship strategy
Considering the potential impact of ATM-AVI to address unmet needs, and the scarcity of other products, safeguarding the effectiveness of ATM-AVI through stewardship is key. Instead of implementing product-specific stewardship measures,
Pfizer publicly reports adopting a portfolio-wide stewardship strategy (see box-out
below).51 With ongoing data collection for Pfizer’s large surveillance database, ATMAVI is already covered by this strategy.43
Overall, Pfizer reports clear plans on equitable pricing, paediatric formulations,planned registration in China and portfolio-wide stewardship. Beyond this, it isunclear how ATM-AVI will be made accessible for patients living in the 113 LMICs in
scope that urgently need the product to overcome resistant bacterial infections.
Pfizer’s portfolio-wide stewardship programme
Pfizer endorses a portfolio-wide stewardship strategy, which includes:
1.	Raising awareness and dissemination of information, including activities to ensure physicians
understand the label indications of its anti-infectives products.
2.	Surveillance through its ATLAS database – a large global AMR surveillance programme.
3.	Grants to support local studies, education and other stewardship initiatives.
4.	Promoting appropriate use by physicians and patients through the development of comprehensive plans for each antibiotic.

FIGURE 6 Through the ‘Accord for a Healthier World’, access to ATMAVI could be facilitated in countries with a high burden of disease
The map depicts the countries that have the highest number of deaths
due to respiratory and intra-abdominal infections.* The majority of patientsthat die from these infections live in LMICs, specifically sub-Saharan Africa(SSA). Pfizer covers most of SSA through its ‘Accord for a Healthier World’.
If included in the Accord, ATM-AVI will be offered on a not-for-profit basis
to these countries.

AbbVie HQ
New York, US● High burden of lower
respiratory infections● High burden of
intra-abdominal infections● High burden of lower
respiratory infections andintra-abdominal infections■ Clinical trials present in
LMICs for adult populations■ Clinical trials present in
LMICs for adult andpaediatric populations
Within geographical scope of'Accord for a Healthier World'

The number of deaths in children under
the age of five due to respiratory and intraabdominal infections is highest in subSaharan Africa.

*The map depicts the burden of disease
in terms of mortality from lower respiratory infections and all related infectionsin the thorax (LRI+) and intra-abdominal infections (IAI). Therefore, it does notshow pathogen-specific or resistance-specific burden of disease. Countries witha high burden of disease were included
based on a threshold of 160 deaths per
100,000 people for LRI+ and 40 deaths

per 100,000 people for IAIs, since LRI+
are more deadly. Please note that due tothe scale of the map, some countries witha high burden of disease or resistancemight not be visible.

Source: Burden of disease: IHMEMICROBE database, trial location: NIH
Clinical Trials

20

Access to Medicine FoundationC A SE S T U DY 3

Venatorx accelerates access to new antibiotic via global
licensing strategy
Cefepime-taniborbactam, a beta-lactam / beta-lactamase inhibitor (BL/BLI) combination antibiotic, is being developed for the treatment of complicated urinary tract
infections (cUTIs) including pyelonephritis. Despite positive Phase III trial results,a New Drug Application (NDA) submission was rejected by the US Food and Drug
Administration (FDA) in February 2024 due to insufficient data on chemistry, manufacturing, and controls (CMC), testing methods and manufacturing processes. In parallel, Venatorx is pursuing approval to treat patients with hospital-acquired bacterial
pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP). Throughexclusive voluntary licensing deals and development partnerships, Venatorx is aiming
to provide adult and paediatric populations with access to cefepime-taniborbactam
in all regions of the world, including low- and middle-income countries (LMICs). No
early access programmes are currently reported to be in place.

Product
Cefepime-taniborbactam
Target pathogen(s)Multidrug-resistant gram-negative bacteria,
most notably carbapenem-resistantEnterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA)
Target indication(s)cUTI (including pyelonephritis), HABP/VABP
Mode of administration
IV
Phase

Overview of countries that are included in current strategies• Adult formulation for cUTIs, including
pyelonephritis: Phase III (completed)2018

In September 2018, Venatorx entered into an exclusive license agreement with China-based Everest Medicines, which has the rights todevelop and commercialise cefepime-taniborbactam in China, Hong
Kong, Macau, Taiwan, South Korea, Indonesia, Malaysia, Philippines,

In April 2020, Venatorx and the Global Antibiotic Research &Development Partnership (GARDP) announced a collaboration to accelerate the development of, and access to, cefepime-taniborbactam for
adult and paediatric populations. This collaboration includes financial
resources, paediatric development and a licensing agreement (seebelow). GARDP holds the exclusive commercialisation rights for both55

the adult and paediatric formulations of cefepime-taniborbactam in 64

Phase III (cUTIs): Brazil, China, Mexico, Peru

Funding partners
2013: Up to USD
21.2 million by
NIAID52
2013: USD 8.9
million by the
Wellcome Trust53
2019: USD 20.7

worldwide, and the public markets in India and South Africa.

million by BARDAIn November 2023, Venatorx entered into a licensing agreement withMelinta Therapeutics to facilitate a strategic partnership and commercialise cefepime-taniborbactam in the US.58

2024

Clinical trials in LMICs in scope

LMICs (the majority being low- and lower-middle-income countries)
55

2023

III (initiated, not yet recruiting)and Ukraine

Thailand, Singapore, and Vietnam.

57

2020

• Adult formulation for HABP/VABPs: Phase

In January 2024, Venatorx and Menarini Group entered into an agreement under which Menarini has the exclusive rights to commercialise
cefepime-taniborbactam in 96 countries in Europe, Latin America,
Middle East, Turkey and North Africa and the Commonwealth of
Independent States (CIS).59

GARDP’s access pathway for cefepime-taniborbactam
In 2020, GARDP and Venatorx started a collaboration to provide access to cefepimetaniborbactam and to accelerate access to the product for paediatric populations.
To accelerate clinical development, GARDP financially supported the Phase III
trial. In addition, GARDP will lead the paediatric development of cefepime-taniborbactam upon its approval by US FDA. By working with Venatorx and other key
partners, such as the Penta Foundation – a global paediatric infectious diseases(with possible
additional funding
up to a total
cost-share of USD

No contractual

86.8 million)54

provisions on access

2020: Up to USD
35 million by
GARDP55and stewardshipplanning reported aspart of these funding announcements

2022: USD
72.1 million(with possible
additional funding
up to 318 million
USD in total) by
BARDA under a
Project BioShieldadvanceddevelopment
and procurement
contract.56

research network based in Italy – GARDP has taken initial steps to plan the clinical
trials required by regulatory authorities such as the European Medicines Agency(EMA) and the US FDA to gain paediatric approval. Data from these trials will also
be used to inform and facilitate paediatric registration filings in LMICs.
To ensure access and affordability of adult and paediatric formulations of21

Antimicrobial research & development

cefepime-taniborbactam, Venatorx has granted GARDP with a license to commercialise and distribute the product in 64 LMICs and the public markets of India andSouth Africa. For the 64 LMICs, GARDP reports cefepime-taniborbactam will be
supplied through the support of an international procurement agency and via anexport waiver. The access strategy for India and South Africa will depend on thecapacity of GARDP and Venatorx to find a single commercialisation partner withknowledge of both markets to efficiently address them together.
Together with key stakeholders, GARDP started to identify the countries with ahigh burden of carbapenem-resistant bacteria and hospitals where cefepime-taniborbactam will have added value. Initially, a phased and monitored introduction in a
few countries, where the product has been identified as high priority for hospitals,
is planned to better understand how the product can be used appropriately, and forwhich patients. In turn, the hospitals can act as hubs to support and share learnings
with less-developed healthcare facilities that plan to introduce the product further
down the line. After the phased introduction, the next step would be to work withan international procurement agency to expand access and to cover parts of the
distribution, which may lead to greater affordability and more sustainable supply.
GARDP is also undertaking surveillance studies of carbapenem-resistant bacteria
in select GARDP territories. In addition, Ventatorx reports it has completed a microbiological surveillance programme of five years and will continue this programme inaccordance with regulatory requirements upon approval.
Licensing partners hold cards to reach patients in LMICs
Overall, Venatorx has granted exclusive licences to its partners for 105 of the 113
LMICs in scope of this report, which include all countries with the highest burdenof carbapenem-resistant E. coli and P. aeruginosa (see map). While GARDP prioritises access for paediatric populations; the public markets of India and South Africa;and 64 LMICs after market approval is achieved, it is unclear how access in other
LMICs within other licensing territories will be planned for. However, it is clear thatthrough exclusive voluntary licensing deals and development partnerships, Venatorx
is aiming to provide adult and paediatric populations with access to cefepime-taniborbactam in all regions of the world.

FIGURE 7 Global partnerships broaden access to cefepime-taniborbactam forpatients in need
The map depicts the countries that have the highest number of deaths due to carbapenem-resistant Escherichia coli and Pseudomonas aeruginosa.* While waiting
for the approval of cefepime-taniborbactam, Venatorx entered four licensing deals
and/or development partnerships. This way, Venatorx is able to accelerate access incountries with a high burden of carbapenem-resistant infections.

GARDP HQ
Venatorx HQMelinta HQ

Menarini HQEverest Medicines HQ

GARDP holds the license for● High burden carbapenemresistant P. aeruginosa (CRPA)● High burden carbapenemresistant E. coli
● High burden carbapenemresistant P. aeruginosa (CRPA)
and carbapenem-resistant E. coli

64 LMICs globally. Of those,
48 are in sub-Saharan Africa
and Asia, where the disease
burden is the highest.

■ Clinical trials present in LMICs*A threshold of 0.69 deaths per 100,000
people due to carbapenem-resistant E.
coli and carbapenem-resistant P. aeruginosa - which could cause cUTIs, HABP/

VABP and other infections - was used
to depict countries with a high burden.
Please note that due to the scale of themap, some countries with a high bur-den of disease or resistance might not
be visible.

Source: Burden of disease: IHMEMICROBE database, Trial location: NIH
Clinical Trials

22

Access to Medicine FoundationC A SE S T U DY 4

Plans for Innoviva’s oral formulation to treat gonorrhoea
target countries with high burden
Innoviva is currently preparing the New Drug Application (NDA) for zoliflodacin, afirst-in-class antibiotic for uncomplicated gonorrhoea, to be submitted within theupcoming year to the US Food and Drug Administration (FDA). Uncomplicatedgonorrhoea is caused by Neisseria gonorrhoeae, which is listed as a high priority
pathogen for antibacterial R&D by WHO. Due to its oral formulation, zoliflodacin
7

offers ease of administration compared to the current standard of care, which isan intramuscular injection of ceftriaxone.18 This is especially relevant for paediatricProduct
Zoliflodacin
Target pathogen(s)N. gonorrhoeae (third-generation cephalosporin resistant and/or fluoroquinolone
resistant)populations.

Target indication(s)Zoliflodacin’s access and stewardship planning centred around GARDP

Mode of administration

partnership

Oral

Innoviva and the Global Antibiotic Research & Development Partnership (GARDP)
formed a partnership to ensure equitable access to zoliflodacin and its appropriate use. The partnership commenced in 2017 between GARDP and Entasis
Therapeutics, later acquired by Innoviva in 2022 and integrated into GARDP’s corebusiness in 2023. Within this partnership, GARDP plays a key role in the development as well as the commercialisation of zoliflodacin. In consultations for thisGonorrhoea

Phase
Adult and paediatric formulations: Phase III(completed)
Clinical trials in LMICs in scope
Phase III: South Africa and Thailand

report, Innoviva indicated that the submission of a comprehensive NDA in the US

Funding partners

will serve as a crucial first step and springboard for subsequent registration filings

National Institutein other countries, particularly within countries for which GARDP has obtained
a license. To already provide patients with access to zoliflodacin prior to market
approval, GARDP reports it is currently setting up an early access programme.
Partnership accelerates clinical development and prioritises access forchildrenof Allergy and
Infectious Diseases(NIAID) sponsored
the Phase II trial
GARDP sponsored
the Phase III trial

No contractual
provisions onaccess and stewardship planning
reported as partof these funding
announcements

The clinical development of zoliflodacin gained traction as GARDP took on the
responsibility to finance and lead the Phase III trial. This trial was the largest clinical
trial conducted for a new gonorrhoea treatment to date, enrolling a total of 930
patients, including women, adolescents, and people living with HIV – somethingthat would have been a challenging undertaking without GARDP.60 By taking thenecessary preparatory steps during clinical development, GARDP aims to eliminate
market inequities by ensuring accessibility for both adult and paediatric patients.
GARDP’s prioritisation of access for paediatric patients is evidenced by the inclusion of patients aged 12 – 17* in the Phase III trial.
GARDP secures manufacturing and commercialisation rights in all low-income
countries
Through a licensing agreement, GARDP has acquired the rights to register andcommercialise zoliflodacin in more than three-quarters of the world’s countries,
including all low-income countries, most middle-income countries, and several
high-income countries. Innoviva retains the commercial rights for zoliflodacin in the
major markets in North America, Europe, Asia-Pacific, and Latin America. Innoviva’s
first step is to pursue registration in the US while also evaluating opportunities forregistration filings in Europe.
GARDP is prioritising registration filings in both South Africa and Thailand initially, given their involvement in the successful Phase III trial. These countries are
situated in regions that face some of the highest burdens of drug-resistant gonorrhoea, specifically in sub-Saharan Africa and South-East Asia. Once Innoviva has
filed for registration in the US, GARDP plans to seek registration in other countries
battling drug-resistant gonorrhoea, with South-East Asia identified as a primary*Patients under the age of 12 were
excluded from the trial as agreed with the
US FDA. The decision was based on the
low prevalence of gonorrhoea in patients
aged 0–12, making their inclusion in thetrial impractical.

23

Antimicrobial research & development

target region. GARDP reports that it intends to introduce zoliflodacin in a mannerthat ensures access in the public sector, and that this commitment applies to any
future countries where it seeks registration.
Beyond an assessment of disease burden data, GARDP collaborates closely withlocal ministries of health and consults local stakeholders to assess whether zoliflodacin is a priority product for countries. Some countries that GARDP has consulted
already have a few indicators of sexual and reproductive health and rights (SRHR)
policies in place. These indicators are helpful to understand whether zoliflodacin
would be beneficial in their local context and can inform GARDP’s future registration filings.
Manufacturing partnerships needed to prepare for demand
GARDP currently holds the manufacturing license for zoliflodacin and will, together
with Innoviva, explore approaches to global commercialisation. While Aurigene
Pharmaceutical Service Limited has been the manufacturing partner for the Phase
III trial, a manufacturing partner for commercialisation has not been announced yet.
Furthermore, Innoviva is actively scoping potential strategic partners who could
contribute to broadening the regulatory reach of zoliflodacin, particularly in territories not covered by GARDP and not prioritised by Innoviva. Innoviva has indicatedthat specific market expertise in such countries, and regulatory experience, will be
key attributes in a potential partner. These partnerships hold potential for improving affordability through scaling supply and expanding access to zoliflodacin beyond
the geographic scope of current distribution networks.

FIGURE 8 Global need for zoliflodacin as gonorrhoea is a widespreadand growing problem
The map indicates the countries that have the highest burden attributable
to fluoroquinolone-resistant Neisseria gonorrhoea, measured by disability
adjusted life years (DALYs).* By partnering with GARDP, Innoviva is able toexpand the global reach for zoliflodacin.

GARDP HQ
Innoviva HQ● High burden of fluoroquinolone-resistant
N. gonorrhoeae

GARDP has market rights in more than three-■ Clinical trials present in LMICs

quarters of the world’s countries, including all lowincome countries, most middle-income countries,and several high-income countries.

*A threshold of 0.95 DALYs was used todetermine countries with a high burdenof gonorrhoea. DALYs were chosen as theunit of measurement because while mor-tality is low (0.5% to 3% of untreated infections) gonorrhoea can cause serious, lifelong consequences in men and women.
Please note that due to the scale of themap, some countries with high burden of
disease or resistance might not be visible.

Source: Burden of disease: IHMEMICROBE database, Trial location: NIH
Clinical Trials

24

Access to Medicine Foundation

Pre-emptive access planning but detailed stewardship planning still required
Collaborating with GARDP has accelerated the development of zoliflodacin, illustrated by the positive top-line results achieved in the Phase III trial, bringing it closer
to the finish line. In similar fashion, outsourcing the commercialisation to GARDP
for most LMICs has resulted in a clear approach towards access. This is illustrated
by GARDP’s commitment to register in clinical trial countries, including paediatricpopulations in clinical trials; actively searching for manufacturing partners; andidentifying countries with high unmet medical need. Within GARDP’s territory, it
is evident that patients facing the highest disease burden will be prioritised whenplanning for access, irrespective of their age or where they live. In addition, GARDP
is currently undertaking research to help inform affordable pricing points to support
access, including in the public sector.
However, there is currently no formal stewardship plan in place for zoliflodacin.
Considering that nearly 100 million people worldwide are diagnosed with gonorrhoea annually, prescriptions for zoliflodacin will be widespread.61 It is therefore
critical that Innoviva and GARDP ensure detailed stewardship plans are put in place
to safeguard zoliflodacin’s long-term effectiveness.

25

Antimicrobial research & development
C A SE S T U DY 5

F2G, with its partner Shionogi, builds foundation that could
shape robust access and stewardship plan for innovative
antifungal agent
F2G, a UK-based small- and medium-sized enterprise (SME), is prioritising its efforts
to obtain US Food and Drug Administration (FDA) approval for its Phase III product,
olorofim. Targeting invasive fungal infections – including invasive aspergillosis caused
by Aspergillus fumigatus – this antifungal aims to benefit patients who have limited
or no remaining treatment options. A. fumigatus is listed as a critical priority pathogen for antifungal R&D and belongs to the group of fungal pathogens that have thehighest public health burden according to the World Health Organization (WHO).8 No
access and stewardship plans have been developed to date. However, through a stra-

Product
Olorofim
Target pathogen(s)Aspergillosis spp., Scedosporium spp.,
Lomentospora spp. and Coccidioides spp.
Target indication(s)Invasive fungal infections, including invasive

tegic partnership with Shionogi – a Japanese research-based pharmaceutical com-aspergillosis

pany – the two companies are collaboratively laying the foundation for what could

Mode of administration

shape up to be a robust access and stewardship plan. Specifically, the companies
have contractually agreed to establishing a concrete access and stewardship plan
within the first 60 days of the first global sale of olorofim.
Shionogi takes on responsibility for clinical trials, registrations, manufacturing,and commercialisation across nearly 80 countries
Given that invasive fungal infections affect patients all over the world, ensuring

Oral
Phase
Adult formulation: Phase III (ongoing)
Clinical trials in LMICs in scope
Phase III: Brazil, China, Egypt, Thailand andVietnamwidespread access to olorofim is critical, especially since resistance to current

Funding partners

treatments with azoles is increasing. Anticipating this need for global access, F2G

None identified

partnered with Shionogi in 2022 to plan for wider reach. As part of the partnership,
Shionogi is responsible for clinical trials, subsequent registration, supply, and commercialisation of olorofim in 79 countries, spanning Europe and Asia, and including
20 low- and middle-income countries (LMICs), such as Thailand and Vietnam. In
partnering, they will share responsibility for access and stewardship planning acrossLMICs, which can allow for wider access to olorofim when it is launched.
Choosing a partner with access and stewardship planning expertise
Small- and medium-sized enterprises (SMEs) that are considering strategic collaborations in thedevelopment and marketing phases of a project can look to potential partners with demonstrated expertise in access and stewardship planning. F2G has cited Shionogi’s approach towards
this as one of the key reasons for its partnership with the company, stating that Shionogi
demonstrated a distinct capability in achieving a careful balance between access and stewardship in its previously devised plans for cefiderocol. For example, Shionogi prioritises working
closely with healthcare facilities and physicians to ensure appropriate use of its products. In thecase of cefiderocol, the company conducted questionnaires to better understand how physicians
intended to use the product to choose the most suitable physicians to partner with.

Bridging barriers through licencing agreements
While Shionogi can share the risks and costs of olorofim’s development, its capabilities to bring the product to local LMIC markets is limited. Shionogi lacks a global
footprint, and its manufacturing is based solely in Japan. As with its access strategy
for cefiderocol (also see box-out above), Shionogi is exploring collaborations, including sub-licencing agreements, with generic medicine manufacturers to address thesechallenges. Specifically, the company aims to address the unmet need in countries,
where the burden of fungal infections targeted by olorofim is high.
In addition, an early access programme is in place to provide patients with accessto olorofim prior to market approval. Due to issues of high demand and stewardshipconcerns, the programme was temporarily halted in 2023, but it is now running again.
Associated risks of olorofim may limit markets where drug will be registered
Due to the associated risk of drug-induced liver injury, patients undergoingtreatment with olorofim need to be closely monitored, which requires a suitable

26

Access to Medicine Foundation

healthcare infrastructure. As a result, the markets where F2G and Shionogi willseek registration are limited. To ensure the appropriate use of olorofim, F2G andShionogi will introduce olorofim in secondary and tertiary healthcare facilities. Thisis likely to impact the accessibility of olorofim in LMICs, especially in hard-to-reachrural areas that may be far from national secondary or tertiary healthcare facilities.
Furthermore, F2G will implement responsible promotion to encourage stewardship;
specifically, the label of olorofim will indicate that it is intended only for patientswith limited or no remaining treatment options.
60-day commitment from first sale is key to reaching LMICs
Partnering with Shionogi has spurred the development of olorofim, with both companies taking initial steps to identify barriers to access and stewardship. However,the lack of concrete access and stewardship planning during development is likely
to delay access to olorofim for patients living in LMICs.
As yet, an access plan that prioritises populations and countries with high unmet
medical needs and addresses patients’ ability to pay is lacking. Therefore, it isunclear which LMICs will be prioritised for product registration after global launch.
Although stewardship plans have not yet materialised, their importance played acrucial role in F2G’s selection of Shionogi as a partner.
The commitment to develop a comprehensive access and stewardship plan
within 60 days of olorofim’s first sale will be key to reaching patients in LMICs.
Given the potential licensing agreements with generic manufacturers; the carefulconsiderations around stewardship; a refurbished early access programme; andShionogi’s expertise in Asian markets, there is potential to make this partnership forco-development an impactful one for patients in LMICs as well, but the uptake isanticipated to be significantly delayed.

FIGURE 9 Respiratory infections caused by fungal pathogens costing
lives in sub-Saharan Africa
The map indicates the countries that have the highest number of deaths
attributable to respiratory infections caused by fungal pathogens.* Thehigh burden in sub-Saharan Africa underscores the need for access andstewardship planning for olorofim within this region.

F2G HQ
Shionogi HQ● High burden of fungal lower
respiratory infections■ Clinical trials present in LMICs
LMICs covered under Shionogi's
licensed territory

Shionogi has market rights in approximately 79
countries, spanning across Asia and Europe. This
includes 20 LMICs, such as Thailand and Vietnam.

*A threshold of 2.25 deaths per 100,000
people was used to determine countries
with a high burden of lower respiratory
infections and all related infections in thethorax caused by fungal pathogens. Please
note that due to the scale of the map,
some countries with a high burden of disease or resistance might not be visible.

Source: Burden of disease: IHMEMICROBE database, Trial location: NIH
Clinical Trials

27Antimicrobial research & development

ANALYSIS: WI D E R R&D L AN DSCAPE

Are funders promoting access andstewardship planning?
The majority of the projects analysed in the preceding case studies are being
developed with the support of partner funding, including the Biomedical Advanced
Research and Development Authority (BARDA), the Global Antibiotic Research &Development Partnership (GARDP), the National Institute of Allergy and Infectious
Diseases (NIAID), the Innovative Health Initiative (IHI) and the Wellcome Trust.
Public and private organisations such as these – as well as the AMR Action Fund,
the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator(CARB-X), and the Novo Repair Fund – are investing vast financial resources
towards antimicrobial R&D.
By providing such ‘push incentives’ (see sidebar alongside) for drug discovery
and product development, these players occupy a unique position in the antimicrobial R&D space, with the opportunity to set contractual provisions that foster andmandate access and stewardship plans.

Antimicrobial R&D will need more than apush to catch up
Current push incentives from R&D funders
are oftentimes geared towards small- andmedium-sized enterprises (SMEs) that face‘valleys of death’, where funding received
during the earlier stages of R&D runs out.
While this push funding is vital within thecontext of a very dry antimicrobial pipeline,
it cannot serve as a replacement for thecurrent lack of pharmaceutical companies’
investment in antimicrobial development.
While many pharmaceutical companies
invest in the AMR Action Fund, for example,
there is consensus that current push funding
incentives are not sufficient to address theFunders are uniquely placed to incentivise access and stewardship planning
Currently, CARB-X and the Wellcome Trust are the only key players for which clear
access and stewardship planning requirements in contractual agreements with
grantees are identified. However, GARDP typically develops and implements its
own access and stewardship plans when partnering with companies. Furthermore,

antimicrobial R&D gap. In the long term,
push incentives need to be met with ‘pull
incentives’, whereby successful antibiotic
developers are ensured future revenues fortheir developed products.

the Novo Repair Fund requires product developers to commit to developing suchplans by the time projects enter late-stage clinical trials. While vaccines to prevent
viral infections fall outside the scope of this report, the Coalition for Epidemic
Preparedness Innovations (CEPI) embeds contractual provisions for equitable
access into each of its vaccine development funding agreements.62
In the case of CARB-X, grantees are obliged to develop these plans when reaching pivotal clinical trials (see box-out below).
CARB-X requires development of access and stewardship plans for early-stage funding it
providesThe Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) has
clear access and stewardship planning funding requirements for its grantees. These grantees
are required to develop an access and stewardship plan for low- and middle-income countries(LMICs) based on the Stewardship and Access Plan (SAP) Development Guide within 90 days
their product entering Phase III trials (or Phase IIb trials, if they are intended as the pivotal trials
to support registration).
If market approval is achieved, CARB-X publishes the developed access and stewardship planon its website.63 This accountability mechanism allows third parties, such as governments andcivil society, to critically assess the plan and its implementation by the company. It must be notedthat beyond the formal development of these plans, CARB-X does not evaluate the quality ofthese access and stewardship plans. However, CARB-X reports that its grantees are obliged towork with the Wellcome Trust, one of CARB-X’s founding funders, to implement their plan.
Where companies do not live up to their contractual obligation to develop and implement anaccess and stewardship plan, the Wellcome Trust has the legal right to take the intellectual property for the purpose of making the product available in markets not prioritised by the company,
and potentially license the product to enable generic access.
CARB-X’s approach demonstrates that even if funding is only directed towards pre-clinicaland early clinical development, access and stewardship requirements can still be contractuallyrequired if a project reaches pivotal clinical trials.

28

Access to Medicine Foundation

The Wellcome Trust mainly provides indirect R&D funding through CARB-X, GARDP
and the AMR Action Fund. It has previously made direct investments in companies,
though these occurred prior to the release of the Stewardship and Access Plan
(SAP) Guide in 2021 (also see p.15). In line with the Wellcome Trust’s principles
of honouring existing contracts, the publication of this guide did not lead to any
retrofitting of these contracts to include access and stewardship planning provisions. After becoming a founding funder of CARB-X, the Wellcome Trust moved
away from investing in companies directly and mandates access and stewardshipplanning through CARB-X. In addition, the Wellcome Trust incorporates access andstewardship requirements directly in its funding agreements with developers aspart of open funding programmes. For instance, the Wellcome Trust establishedthe Advance ID Clinical Research Network in Southeast Asia, where new funding isprovided to support a clinical trial for an antibiotic.64 As part of this funding agreement, access and stewardship planning will be required by the developer.
To increase access and guarantee stewardship, GARDP enters into collaborative agreements with antibiotic developers, particularly small- and medium-sizedenterprises (SMEs), and provides expertise and financial support to help derisk drug
development. While GARDP doesn’t require portfolio companies to formally agree
to developing access and stewardship plans, it prioritises access through these
agreements whereby GARDP develops and implements the access and stewardshipmeasures, in turn reducing the burden on SMEs.
In its operations, the AMR Action Fund sets itself apart from other fundingorganisations. Instead of providing non-dilutive funds, the AMR Action Fund operates as a private investing vehicle by making public health guided equity investments in SMEs. As such, the AMR Action Fund, which is mainly funded by industry,is the largest public-private partnership investing in SMEs that develop antimicrobial therapeutics. The AMR Action Fund clearly sets out access and appropriate
use principles that should be agreed upon by its portfolio companies.65 However,whether these principles are contractually binding or enforced is unclear.
Grants by US and EU lack provisions on access and stewardship
It is important to note that funders may have different reasons for the lack ofaccess and stewardship requirements as part of funding provisions. For instance,
NIAID, which is part of the National Institutes of Health (NIH), and BARDA, which ispart of the Administration for Strategic Preparedness and Response, both receive
appropriations from the US Congress. These appropriations mandate NIAID andBARDA to fund early-stage and late-stage R&D respectively (see Figure 10 on p.30).
Requirements such as access and stewardship planning are established at thenational and state level based on guidance from the US Centers for Disease Control(CDC) and state health authorities.66 As no access and stewardship requirements
are part of this mandate, BARDA does not enforce such planning in its funding
requirements with grantees.
Similarly, funding by the European Union (EU) is primarily provided to target unmet medical needs of and ensure access to innovative medicines for
European citizens. The funding process is organised via specific projects, such as‘COMBACTE-CARE’ or the ‘AMR Accelerator’, under the ‘Innovative Health Initiative’(former ‘Innovative Medicines Initiative (IMI)). Despite the commitment by EU’s
Health Emergency Response Authority (HERA) to increase access to medicines in
LMICs, specific access and stewardship requirements beyond the EU scope could
not be identified.67

29

Antimicrobial research & development

Fragmented funding requires transparency to help monitor access andstewardship planning
The various funders in the antimicrobial space tend to focus on specific phasesof the R&D process, which means that funding is fragmented across the productdevelopment process (see Figure 10). As a result, the level of access and stewardship planning required by funders may vary, depending on the stage of development
they are supporting. However, funders can still help guarantee access and stewardship planning, regardless of the phase that is being funded.
To ensure that qualitative access and stewardship planning will be implemented
effectively throughout clinical development, funders can set provisions to be transparent on outcomes post funding. In addition, it is vital for funders themselves totransparently report on actions that have been taken. Currently, the lack of clarity
in this regard makes it difficult for early-stage funders to follow up and ensure plans
will be implemented; conversely, without clear information on what has been set
out in the early stages, late-stage funders will find it difficult to build on what has
already been done (or not). In addition, transparency on actions can offer learnings
to funders who are still working to incorporate access and stewardship planning incontractual agreements. Importantly, overall transparency can help to level-set thefunding landscape towards a more harmonised standard on access and stewardshipplanning. This will also make it easier for companies to navigate the funding landscape, as they will not have to adjust to various new funder requirements.

FIGURE 10 Funders provide push incentives across all phases ofdevelopment to refuel the antimicrobial pipeline
This figure depicts some of the most prominent funding organisations in
antimicrobial R&D.74,75 As these organisations provide a vast number ofresources to stimulate capacity building, therapeutics development, or basic
research, they have the opportunity to link funding to access and stewardship provisions.
Funding

Basic

Discovery &(USD)

Research

Preclinical

JPIAMR*

127M

NIH

3.6bn

IMI**

425.91M

CARB-X

405.64M

Novo Repair Fund

165M

BARDA

347.69M

AMR Action Fund

Unknown

GARDP

79.44M

Data includes all reported AMR-related
R&D funding between 2017 and 2023. Asa closed-end fund, the budget of the Novo
Repair Fund was set up in 2018 – however, funding is still ongoing.

*Will become part of EU One Health AMR
Partnership in Q1 2025.

CommercialiPhase I

Phase II

Phase IIIsation & Access**Operates as IHI since November 2021.

30

Access to Medicine Foundation

KE Y FI N D I NGSStructured advance planning for access andstewardship has not become the norm yet
As has been identified in the Foundation’s research through its AMR Programme,
tackling the sheer scale and pace of drug resistance is a complex global health issue
that will require action from pharmaceutical companies across several areas. But
failure to provide appropriate access to and implement stewardship measures tosafeguard the effectiveness of innovative antimicrobials anywhere will inevitably
limit efforts to tackle resistance everywhere.
By acting now, companies can save lives and help address rising levels of AMR.
Gaps and opportunities: Which efforts can be scaled and what shortcomings
need to be addressed?
Based on the analysis of the case studies in this report, the Foundation has identified that detailed access and stewardship planning during late-stage developmentof antibiotics and antifungals has not become standard yet. Four findings gleaned
from the Foundation’s assessment highlight examples of positive steps that are
being taken, as well as gaps that need to be addressed. These insights can help toensure that the much-needed antibiotics and antifungals in the pipeline reach theestimated 1.27 million people who die annually from drug resistant infections.
1. Concrete plans for registration are lacking for almost all LMICs
Filing for registration is a vital first step towards introducing a medical productinto a country, as successful registration means that a product is allowed to beimported and sold. However, for all five projects combined, concrete commitments for registration could only be identified for five low- and middle-income
countries (LMICs) – China, India, Mexico, South Africa and Thailand. Most ofthese planned registrations are the result of post-trial commitments by developers to register in countries where clinical trials are being conducted. As a result,for 108 LMICs it is unclear whether any of the five projects in scope will be madeavailable upon initial approval. Yet, it must be noted that the Global Antibiotic
Research & Development Partnership (GARDP) plans to provide access to
cefepime-taniborbactam (Venatorx) in 64 LMICs through export waivers and aninternational procurement agency.
2. Affordability and stewardship in LMICs are largely overlooked during
planning
Affordability and stewardship are challenging factors for companies to widen
access to new antibiotics and antifungals in LMICs. With strict stewardshiprequirements but low profitability, new antibiotics and antifungals are notintroduced at scale. While Pfizer applies specific pricing strategies for aztreonam-avibactam – and offers products in its portfolio at a not-for-profit basis
through its ‘Accord for a Healthier World’ initiative – no concrete plans for making new products affordable to patients in any LMIC could be identified in theother four case studies in this report.
In addition, besides large companies like GSK and Pfizer who havecomprehensive surveillance programmes in place, detailed plans to ensure
appropriate use – for example, by responsible promotion and ensuring
supportive diagnostics – were lacking across the board. Stewardship planning

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through strategies like these not only helps with ensuring that patients receive
the right treatment, but also serves companies by preserving the efficacy of theirown products that are marketed.
3. Paediatric trials prior to market approval are a hopeful sign for children
In 2019, 1 in 5 people who died from drug-resistant infections was a child under
5 years of age. However, market approval for paediatric use typically takes up
to ten years longer than adult use, which is why it is crucial to consider paediatric populations during, and not after, drug development. Of the five companies featured in the case studies, four are conducting or initiating clinical trials
involving children, including GSK, Pfizer, Innoviva, and Venatorx – with Innoviva
and Venatorx doing so with support from the Global Antibiotic Research &Development Partnership (GARDP). This is especially notable for the projects
by Venatorx and Pfizer, as both are listed on the World Health Organization
Paediatric Drug Optimisation for Antibiotics (WHO PADO) list, which prioritises
the antibiotics in development that are urgently needed for children. The efforts
from these four companies to prioritise children early on are positive developments in closing the gap between adult and paediatric access and set an example
of what can be done by other developers.
4. Partnerships help scale efforts, but other tools to broaden access andstewardship plans are underutilised
Small and medium-sized enterprises (SMEs) rely heavily on partners to help
commercialise products and drive global access. Not only are partnerships necessary for survival, but they are also used as a strategy to outsource the challenging task of providing access in LMICs. For example, F2G co-develops its antifungal project with Shionogi, who in turn receives licensing rights in the Asia Pacificregion and Europe. Furthermore, organisations like GARDP – funded by governments and charitable funds – are increasingly taking on the task of access andstewardship planning for LMICs. Without constraints of commercial profitability
requirements, GARDP can prioritise access to new antibiotics for those patients
who need them the most. This is reflected in GARDP’s partnerships for zoliflodacin (Innoviva) and cefepime-taniborbactam (Venatorx), with both case studies
demonstrating great detail on country and population prioritisation, supply chain
planning and the development of additional formulations.
Aside from partnerships with GARDP, companies can set up their own
plans based on the Stewardship and Access Plan (SAP) Development Guide in
2021. This Guide – developed by the Combating Antibiotic Resistant Bacteria
Biopharmaceutical Accelerator (CARB-X) in collaboration with key partners,
including the Wellcome Trust and the Access to Medicine Foundation – supports companies in planning ahead for access and stewardship. However, while
this Guide has been in existence for three years, the companies assessed in thisreport are underutilising the recommendations in this guide.

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Access to Medicine Foundation

SPOTLI G HT

Without the resources and efforts of big
pharma, innovation might never reach all
eligible patients sustainably
Most large pharmaceutical companies have closed their doors on antibacterial andantifungal R&D and minimised their investments to acquire promising small- andmedium-sized enterprises (SMEs). This has not only left a major gap in innovation,
but also a major gap in delivering new products to patients.
While SMEs have become the powerhouses of developing innovative antibiotics and antifungals, these SMEs do not have the resources to commercialise new
products and provide global access. Therefore, early development of innovative
products by SMEs must go hand in hand with late-stage development and scaling ofaccess in low- and middle-income countries (LMICs) by large pharmaceutical companies. These large multinational companies hold a vast array of expertise, capacityand financial resources that are needed to foster late-stage R&D commercialisation.
However, without being acquired by these companies, SMEs are unable to tap into
their much-needed resources. As a result, SMEs seek public funding and collaborations to survive and to outsource the responsibility of ensuring access in LMICs.
To address the gap in R&D left by industry, public and private funders are
increasingly offering push and pull incentives. This funding is vital in stimulating
antimicrobial R&D, however, linking it with access and stewardship provisions is notcommon practice. To bolster access in LMICs, partnerships like the Global Antibiotic
Research & Development Partnership (GARDP) – funded by governments and charitable funds – have stepped in to alleviate the burden of access and stewardshipplanning for SMEs. Without constraints of commercial profitability requirements,
GARDP can prioritise access to new antibiotics for those patients who need themthe most. However, leaving patient access to innovative products in LMICs entirelyin the hands of public and private funders is not a sustainable solution.
Large pharmaceutical companies need to re-enter the ring and make theirunique expertise on access and commercialisation available. While there is a needfor more push and pull incentives to revive the R&D pipeline and make innovationin the AMR space financially sustainable, these companies have a duty to commercialise innovative late-stage projects currently in the pipeline and provide access in
LMICs.
By financially supporting the AMR Action Fund, many large pharmaceutical companies invest in the development of a few novel antibiotics, but this is not enough.
Active engagement is critical – even if that is by actively supporting SMEs. Without
active engagement from more pharmaceutical companies, there is a real risk thatthe world will be left without any antibiotics and antifungals that will be effective
against drug-resistant infections. Not only will this put the lives of millions at risk,
but it will have a direct impact on companies. Without effective antibiotics, many
profitable products that are at the core of companies’ business model – such as
oncology drugs – will be threatened. Therefore, investing in R&D and providing
access to new antibiotics and antifungals will not only help curb AMR, but it will also
safeguard large pharmaceutical companies’ business (also see ‘Recommendations’in the next section of this report).
It is critical for companies to act now and make sure the few antimicrobials are
made available to patients on the frontlines of drug resistance.

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RECO M M E N DATI ONSPrioritising access and stewardship:
How to rethink and redesign R&D
Large pharmaceutical companies andsmall- and medium-sized enterprises• Pursue access and stewardship planning for all late-stage clinical projects for
antibiotics and antifungals, both innovative and adaptive.
• Increase the depth and breadth of access and stewardship plans. Utilise the
Stewardship and Access Plan (SAP) Development Guide to guide the quality ofdeveloped plans▶ Access planning• Develop strategy to file for registration in LMICs. Be inclusive of countries,
especially low-income countries, with particularly high burdens of disease
and disproportionally affected populations, such as children, women andimmuno-suppressed patients.
• Conduct clinical trials in low- and middle-income countries (LMICs). These
trials must be followed by post-trial access commitments, such as filing forregistration.
• Conduct paediatric clinical trials in a timely manner to develop and register
formulations for children.
• Prioritise LMICs for access planning based on public health needs byengaging with stakeholders on the ground to better understand for whichcountries this could be a priority product.
• Set up early access programmes that allow patients with no or limited
treatment options to access antibiotics and antifungals that are not registered yet.
• Establish pricing strategies that consider patients’ ability to pay in LMIC
settings.
▶ Stewardship planning• Set up surveillance programmes for projects in the pipeline and publicly
share this data, or support and engage with external surveillance programmes run by other organisations.
• Ensure supportive diagnostics and susceptibility testing are available assoon as possible. For example, by collaborating with diagnostics companies.
• Commit to responsible promotion either by avoiding the use of sales
agents for antibacterial and antifungal medicines, or by removing the financial incentive linked to sales volumes of these medicines.

Large research-based pharmaceuticalcompanies• Remain engaged in antibacterial and antifungal R&D and align R&D investments
to address the most critical public health needs. R&D investments must target public health priorities and the global burden of disease, for example, byconsulting the World Health Organization’s (WHO’s) Priority Pathogen lists for
antibacterials and antifungals. Investing in R&D includes acquisitions of smalland medium-sized enterprises (SMEs) with promising pipeline candidates.
• Leverage local offices and regional hubs in LMICs to facilitate connections andpartnerships for improved access and stewardship.
• Implement not-for-profit models in LMICs where products have low financial
viability, with the necessary stewardship provisions to ensure safeguarding thelong-term effectiveness of new products, and commit to measuring patientreach with a clear methodology.
• Support access and stewardship planning by SMEs either through licensing
deals, co-development partnerships or acquisitions.

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Access to Medicine Foundation

Small- and medium-sized enterprises• Consider partnerships with large pharmaceutical companies and public partners for co-development, voluntary licensing agreements and access and stewardship planning in LMICs.
• Prioritise partners with a strong presence and a proven track record of successfully bringing products to market in LMICs.

Public funders, including governmentsof high-income countries• Mandate contractual provisions as part of push incentives that require accessand stewardship planning from Phase II onwards. In addition, develop enforcement mechanisms that guarantee quality and implementation of the developed
access and stewardship plans. Existing tools such as the SAP Development
Guide can be leveraged by all funders to harmonise expectations from companies and limit fragmentation of funder requirements.
• Enable direct communication and transparency about agreed-upon access andstewardship obligations between funders to ensure that commitments made in
the past are upheld.
• Foster a secure and sustainable market for antibiotics and antifungals anddevelop policies that encourage and incentivise companies to remain engaged
in the R&D space. Push and pull incentives must be aligned with publichealth priorities identified by WHO while acknowledging country-by-country
differences.
• Support improved transparency and data to measure access in LMICs, such as
the Access to Medicine Foundation.

Governments in low- and middleincome countries• Support clinical trials by companies and reduce the time to issue marketing
authorisation.
• Set up or support surveillance systems to monitor resistance and the use ofantibiotics and antifungals. Governments can help build an ecosystem thatallows for accurate data collection, for example through implementation ofelectronic patient records. If there are financial barriers, explore options forinvestments, such as from the World Bank or high-income countries.
• Invest and engage in regulatory harmonisation schemes, such as collaborative
registration procedures or mutual recognition procedures, to accelerate registration filings by pharmaceutical companies.
• Identify key priority products that are still in late-stage clinical development
and signal the importance of these products internally to regulatory agencies
and externally to companies and key partners, such as the Access to Medicine
Foundation.

Public-private partnerships• Support companies with limited resources and R&D projects that target priority pathogens to ensure novel interventions with low commercial viability reachthe most affected patients.
• Prioritise licensing agreements and/or commercial partnerships, particularly forcountries or regions where there is no commercial interest to seek registration
for a product.

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Antimicrobial research & development

LIST O F AB B REVIATIONS
3CGR Third-generation cephalosporin-resistantA. fumigatus Aspergillus fumigatus
AMR Antimicrobial resistance
AmpR Ampicillin resistance
ATM-AVI Aztreonam-avibactam
BARDA Biomedical Advanced Research and Development Authority
BIO Biotechnology Innovation Organization
BL Beta-lactam
BLI Beta-lactamase inhibitor
BSI Blood stream infection
Campylobacter spp. Campylobacter species
CARB-X Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator =CDC Centers for Disease Control
CIS Commonwealth of Independent States
CEPI Coalition for Epidemic Preparedness InnovationscIAI Complicated intra-abdominal infection
ClaR Clarithromycin-resistant
CMC Chemistry, manufacturing, and controls
CR Carbapenem-resistant
CRAB Carbapenem-resistant Acinetobacter baumannii
CRE Carbapenem-resistant Enterobacterales
CRPA Carbapenem-resistant Pseudomonas aeruginosacUTI Complicated urinary tract infection
DHSC Department of Health and Social CareE. coli Escherichia coli
E. faecium Enterococcus faecium
EMA European Medicines Agency
ESBL Extended spectrum beta-lactamase
EU European Union
FDA Food and Drug AdministrationFQR Fluoroquinolone-resistant
GAMRIF Global AMR Innovation Fund
GARDP Global Antibiotic Research & Development Partnership
GDP Gross domestic product
GNI Gross national income
HABP Hospital-acquired bacterial pneumonia
HERA European Health Emergency Response Authority
HHS Department of Health and Human Services
IAI Intra-abdominal infection
ICU Intensive care unit
IHI Innovative Health Initiative
IHME Institute for Health Metrics and Evaluation
IMI Innovative Medicines Initiative
IV Intravenous
JPIAMR Joint Programming Inititaive on Antimicrobial Resistance
LMICs Low- and middle-income countries
LRBs Large research-based pharmaceutical companies
LRI Lower respiratory infection
LRI+ Lower respiratory infections and all related infections in the thorax
MBL Metallo beta-lactamase
MoA Mode of action
MR Methicillin-resistance
NDA New drug application36

Access to Medicine Foundation

N. gonorrhoeae Neisseria gonorrhoeae
NIAID National Institute of Allergy and Infectious Disease
NIH National Institutes of Health
OGA Office of Global Affairs
P. aeruginosa Pseudomonas aeruginosa
PDUFA Prescription Drug User Fee Act
PNS Penicillin non-susceptible
R&D Research and development
Salmonella spp. Salmonella species
SAP Stewardship and Access Plan
S. aureus Staphylococcus aureus
Shigella spp. Shigella species
SME Small and medium sized enterpriseS. pneumoniae Streptococcus pneumoniae
SRHR Sexual and reproductive health and rights
SSA Sub-Saharan Africa
STI Sexually transmitted infection
UK United Kingdom
US United States
USD US dollar
US FDA US Food and Drug AdministrationUTI Urinary tract infection
uUTI Uncomplicated urinary tract infection
VABP Ventilator-associated bacterial pneumonia
VR Vancomycin-resistance
WHO BPPL World Health Organization bacterial Priority Pathogen List
WHO FPPL World Health Organization fungal Priority Pathogen List
WHO PADO World Health Organization Pediatric Drug Optimization for Antibiotics
WHO World Health Organization

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Antimicrobial research & development

D E FI N ITI O NS
Access plan

Antimicrobial stewardship

Plans to ensure that access needs in low- and middle-income

A systematic and comprehensive process that aims to ensure

countries are taken into consideration during the R&D stage.

that all aspects of prescribing, (e.g., drug, dose, duration),

Access plans can be developed in-house or in collaboration.

dispensing, and the use of antimicrobial medicines are con-

They can include commitments and strategies, as well assistent with the available evidence on how to minimise themore concrete access provisions, such as specific measuresemergence of antimicrobial resistance.

developed in partnership with other organisations that canenforce accountability. Potential components of an accessAppropriate use of antimicrobials

plan include registration commitments, equitable pricing

The cost-effective use of antimicrobials, which maximises

strategies, sufficient supply commitments, and applying forclinical therapeutic effect while minimising both drug-related

World Health Organization prequalification. Access plans

toxicity and the development of antimicrobial resistance.68

facilitate availability, affordability and supply for patients incountries within the scope of the Programme.

Cross-resistance
Cross-resistance refers to the resistance developed to a usu-

AMR surveillance

ally effective antimicrobial medicine through exposure to a

[Working definition, used for analysis]

similarly acting substance. Cross-resistance can occur among

The continuous and systematic collection, analysis and inter-

human antimicrobials and is also observed between humanpretation of antimicrobial infection and resistance-trend data

antimicrobials and products used in animal health or agricul-

needed for the planning, implementation, and evaluation ofture (e.g., pesticides, herbicides or fungicides).

antimicrobial stewardship activities.
Diagnostics
Antibacterial medicine

Diagnostics or diagnostic tests are approaches used in clin-

Antimicrobial medicine used to treat bacterial infections by

ical practice to identify with high accuracy the disease of

directly targeting the bacteria that causes the infection or thea particular patient and thus to provide early and properdisease process (as opposed to targeting the symptoms oftreatment.69

the infection). Biocides are not considered antibacterial medicines. See also Antibiotics.

Disability-Adjusted Life Year (DALY)
A measure of disease burden that combines disease-associ-Antibiotics

ated mortality and morbidity. It is the sum of the number ofEquivalent to Antibacterial medicine. The term “antibiotic” isyears of life lost (YLLs) and years lived with disability (YLDs).

often used inconsistently in literature to denote either a drug

DALYs allow the comparison of disease burden across differ-that targets any type of microorganism in the body or, alter-ent populations and health conditions across time. One DALY

natively, a drug that targets bacteria specifically.

equals one lost year of healthy life.

Antifungal medicine

Early Access Programme

Antimicrobial medicine used to treat fungal infections by

An Early Access Programme is a pathway allowing patients

directly targeting the fungi that causes the infection (asto access medicines that are yet unregistered in a country.

opposed to targeting the symptoms of the infection or toxins

These programmes typically include medicines for serious or

produced by the pathogen).

life-threatening diseases when there are no other treatment
options available, until marketing authorisation has been

Antimicrobial resistance (AMR)

granted.

Antimicrobial resistance is the ability of microbes such asbacteria, viruses, fungi and parasites (protozoa or helminths)

Equitable pricing strategy

to grow in the presence of an antimicrobial substance (e.g., a

A targeted pricing strategy which aims to improve access to

medicine) that would normally kill them or limit their growth.

medicine for those in need by considering the relevant payer’s

Resistance is a consequence of evolution via natural or artifi-

ability to pay, and by taking healthcare systems’ needs andcial selection.

characteristics into account.

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Access to Medicine Foundation

Gram-negative bacteria

Pull incentive

Gram-negative bacteria are bacteria that do not retain the

Pull incentives, in the form of extended exclusivity periods,

crystal violet stain used in the Gram staining method of bac-higher reimbursement or market entry rewards, reward com-terial differentiation due to their bacterial cell wall.

panies for bringing new drugs to the market through lowering
the uncertainty for return on investment.

Innovative project[Working definition, used for analysis]

Push incentive

A novel candidate meets at least one of the four criteria

Push incentives, in the form of grants, partnerships or

defined in WHO’s report “2021 Antibacterial agents in clinicaltax credits, are employed to lower the cost of and de-riskand preclinical development” (2022): (1) new chemical class;research and development of a new medicine.

(2) new target; (3) new mode of action (MoA); (4) absence ofcross-resistance.

Small- and medium-sized enterpriseEnterprises can be classified in different categories according

Pooled procurement

to their size; for this purpose, different criteria may be used,

A process through which a buyer pulls together demand to

but the most common is number of people employed. Small

increase the total quantity of a specific product to include in

and medium-sized enterprises (SMEs) employ fewer than 250

a tender, in order to benefit from better procurement condi-

people and can be subdivided into micro enterprises (fewer

tions and economies of scale.

than 10 employees), small enterprises (10 to 49 employees),
medium-sized enterprises (50 to 249 employees).70

Post-trial access
The continued provision of an investigational product or com-

Stewardship plan

parator to clinical trial participants following the end of the[Working definition, used for analysis]

clinical trial in which they participated when continued treat-

A stewardship plan is a plan set up to ensure that AMR-

ment is beneficial.

relevant public health needs are taken into consideration during R&D. These plans may be developed in-house or throughPriority pathogen

collaborations and include commitments, strategies, concrete[Working definition, used for analysis]

provisions, and other agreed-upon measures (typically devel-

Priority pathogens are pathogens for which new medicines

oped in partnership) to enforce accountability. Stewardshipand vaccines are highly needed. Priority pathogens areplans facilitate the appropriate use of antimicrobial medicines

informed by the bacterial and antifungal priority pathogens

and reduce the emergence of resistance. Examples include

lists published by WHO and are based on unmet R&D needs(but are not limited to) appropriate promotional practices andand public health importance.

conducting surveillance studies.

Product Development Partnership (PDP)

Voluntary licensing[Working definition, used for analysis][Working definition, used for analysis]

Product Development Partnerships (PDPs) take the form of

A voluntary license is an authorization given by the patentcentralised non-profit organisations that facilitate financial

holder to a generic company, allowing it to produce the pat-risk-sharing across the public and private sectors by poolingented medicine or vaccine, often at a lower cost. The licenseand sharing resources, both tangible and intangible, for theusually sets quality requirements and defines the countries indevelopment of medicines, vaccines, and other health tools.

which the licensee can sell the product.71

Public-private partnership

Vulnerable populations

A partnership between one or more public organisation(s)People at greater risk of facing barriers to accessing medi-

and a private sector company or companies for providing acines due to social, economic and/or health considerations.

public asset or service, in which the private party bears significant risk and management responsibility, and remuneration
is linked to performance. The Programme also considers apartnership between a non-profit organisation and the private
sector to be a PPP.

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Antimicrobial research & development

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