By Márcia Costa and Emily May, Managers, Deloitte Centre for Health Solutions

Antimicrobials have drastically changed modern medicine and extended the average human lifespan by 23 years.^[1] However, over the past 30 years there has been a gradual decline in antibiotic R&D with rising levels of antimicrobial resistance (AMR) posing a significant global threat to human health.^[2] In 2019, the World Health Organisation (WHO) estimated that AMR was linked to around five million deaths and if this trend continues, annual AMR-related deaths could reach 10 million by 2050, with an estimated cost of $100 trillion to the global economy.^[3] Although 16 new antibiotics have been approved since 2017, many pathogens still have no treatments as most new antibiotics are associations or improvements of existing molecules, originally discovered over 30 years ago.^[4] There is therefore an urgent need for more innovative mechanisms of action and new chemical classes of antimicrobials. This blog explores recent developments in incentivising antibiotic R&D, the current R&D pipeline and the potential of GenAI in identifying new therapies and reducing the risk of AMR.

The current response to the AMR crisis

AMR occurs when microorganisms, such as bacteria, viruses, fungi, and parasites, evolve and become resistant to the effects of antimicrobial drugs, including antibiotics, antivirals and antifungals. Some bacteria, such as gram-negative bacteria, are multi-drug resistant.^[5] Critical factors contributing to the development of AMR include the overuse and misuse of antimicrobials, and poor infection prevention and control practices. The consequences of AMR pose a significant threat to public health by undermining existing treatments, adding additional risks to procedures such as surgery, caesarean sections and chemotherapy, and increasing the risk of untreatable infections.

Governments, international organisations, and healthcare institutions have recognised the urgent need to implement comprehensive strategies including implementing real-time surveillance and tracking systems and educating healthcare professionals (HCPs) and patients on AMR, the appropriate prescribing and use of antibiotics and the need for rigorous compliance with infection prevention.^[6],[7]

The antibacterial R&D pipeline

Antibiotic R&D slowed drastically after the 1980s and while there have been several regulatory approvals over the past decade, 77 per cent of approvals since 2017 were for antibiotics that belong to existing antibiotic classes for which resistance mechanisms are well known.[^8] In fact, no new class of antibiotics has been discovered since the 1980s; the antibiotics that have been brought to market in the past three decades are variations of drugs that have been discovered before.^[9] This is insufficient to tackle the ever growing threat of the emergence and spread of drug-resistant infections. It is therefore crucial to develop new treatments, particularly those targeting multi-drug resistant bacteria, and incentivise the R&D of new antimicrobial classes.

To coordinate R&D globally, the WHO published the Bacterial Priority Pathogens List (BPPL) in 2017 with 12 antibiotic-resistant priority pathogens, split into critical, high and medium priorities. The list was developed to guide R&D investment for new antibiotics and formed the basis for activities related to surveillance and control of antibacterial resistance.^[10]

In 2024, the WHO published an overview of the 2023 antibiotic R&D preclinical and clinical pipeline (see Figure 1). Positive developments since 2017 include:

• an increase in the number of both traditional and non-traditional agents addressing pathogens listed in the BPPL, including gram-negative broad-spectrum agents
• 12 new traditional antibacterial products entered the clinical pipeline
• 40 non-traditional products (such as immune-modulating and microbiome-modulating agents) entered the clinical pipeline, including 30 that target bacteria included in the BPPL, 13 of which are critical-priority bacteria
• 16 new antibacterials have been approved by a stringent global WHO listed regulatory authority. [11]

Figure 1. Number of traditional and non-traditional antibacterials by clinical development phase

Source: WHO 2023

However, many of the BPPL critical-priority bacteria remain unaddressed, several agents have insufficient evidence of activity against these critical bacteria, prevalence of oral antibacterial formulations (preferable due to ability to take at home) have decreased since 2017 (47 per cent vs 37.5 per cent in 2023) and paediatric indications are still lacking.[12] Moreover, AMR profiles are changing. In response, the WHO has published an update of the BPPL, which now comprises 15 pathogens with a lack of adequate treatment options, including drug-resistant mycobacterium tuberculosis, which as we explored in a blog continues to be a significant public health issue.[13]

The UK and European Union’s approach to incentivising R&D initiatives

The UKs then Conservative government published three five-year plans in 2014, 2019 and May 2024 aimed at tackling AMR. The plans build on one another, with the most recent plan incorporating lessons learned from COVID-19 and setting ambitious targets to drive down inappropriate use of antimicrobials and simulate R&D efforts.[14] The 2019 and 2024 plans also supported the Conservative government’s 20-year vision to contain and control AMR by 2040.

These plans also included proposals for a first-of-its-kind ‘subscription model’ initiative for NHS reimbursement to encourage pharma companies to develop new antimicrobials. This is designed to break the link between the payments received and the number of antimicrobials prescribed, removing incentives for overuse and reducing the risk of resistance development.[15] Following a 2022 pilot scheme, on 12^th August, the NHS issued tenders for contracts with pharma companies for antimicrobials of up to £20 million a year per drug, worth up to £1.9 billion over 16 years, aiming to make it financially viable for pharma companies to develop next-generation antimicrobial drugs.[16]

Meanwhile, the EU Commission have proposed an innovative change in the reform of the EU pharmaceutical legislation which allows pharma companies to earn vouchers for longer regulatory exclusivity for another drug in their portfolio if they develop a novel antimicrobial for priority targets (i.e., those with a significant clinical benefit). While this voucher scheme would delay the market entry of generics, it will be limited to a maximum of ten vouchers that can be granted over 15 years.[17]

However, this is not a challenge the UK, or even Europe, can tackle on its own; drug-resistant infections know no borders. The UN member states are seeking an ambitious agreement at the UN General Assembly (UNGA) high level meeting (HLM) in September 2024 for co-ordinated action to collectively address the looming threat AMR poses.[18]

The potential role for GenAI

There is growing evidence that GenAI is poised to revolutionise healthcare and life sciences. Our research suggests that there are several ways in which GenAI could be applied to AMR and support researchers and clinicians in tackling this issue through:

• Discovery: assisting in the discovery of novel antibiotics by generating and screening chemical compound libraries to identify candidates for further development and stable compounds for improved oral administration.
• Surveillance: analysing large datasets of microbial strains, aiding in the early detection of emerging resistance trends, and monitoring the environmental impact of antimicrobial use to identify sources of resistance development.
• Diagnosis and treatment optimisation: AI can speed up diagnosing the cause of an infection from days to hours and help determine the most effective antimicrobial therapies and doses (including for children), reducing the risk of resistance development.
• Education of HCPs and patients: promoting responsible antimicrobial use and fostering awareness of the importance of combating resistance
• Personalisation: identifying alternative effective treatments to reduce misuse or personalised antibiotic treatments to optimise outcomes, taking into account individual patient characteristics and microbial profiles.

For these to be effective however, the availability of high-quality data on antimicrobials including information on susceptibility and resistance will be essential, as will the need to validate the results from GenAI modelling and application of the concepts in the real world.

Conclusion

Despite clear progress of the development on new antibiotics and antibacterial agents, there is still much to be done to tackle the challenge of AMR. A cross-ecosystem, global approach that incentivises the development of new antimicrobial classes, encourages sensible prescribing strategies and engages governments and institutions is required for progress to be achieved at the necessary pace.

Márcia Costa - Research Manager, Life Sciences Insight Lead

Márcia is the research manager for healthcare in the Centre for Health Solutions, providing support and expertise to develop solutions to overcome today’s healthcare challenges. Working with the team, Márcia develops insights based on rigorous data analysis to improve outcomes for patients and increase health systems efficiencies. Originally from Portugal, Márcia has an MSc in biomedical engineering and biophysics and a PhD in cancer research. Márcia has previously worked in publishing for an oncology journal in London. Márcia is passionate about health equity.

Email | LinkedIn

 

Emily May, Assistant Manager, UK Centre for Health Solutions

Emily is a manager in the Centre for Health Solutions where she applies her background in both scientific research and pharmaceutical analytics to produce supported insights for the Life Sciences and Healthcare practice. Emily leads the research and publication of the life sciences insights, performing thorough analysis to find solutions for the challenges impacting the industry and generating predictions for the future.

Prior to joining the centre, Emily worked as an Analytical Scientist conducting physical chemistry analysis on early stage drug compounds and previously lived in Antwerp, Belgium where she researched and developed water-based adhesive films.

Email | LinkedIn

 

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[2] Antibiotics: past, present and future - ScienceDirect

[3] https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance

[4] https://iris.who.int/bitstream/handle/10665/376944/9789240094000-eng.pdf?sequence=1

[5] https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance

[6] EU Action on Antimicrobial Resistance - European Commission (europa.eu)

[7] https://www.gov.uk/government/collections/antimicrobial-resistance-amr-information-and-resources

[8] https://iris.who.int/bitstream/handle/10665/376944/9789240094000-eng.pdf?sequence=1

[9] https://www.gov.uk/government/collections/antimicrobial-resistance-amr-information-and-resources

[10] https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed

[11] https://iris.who.int/bitstream/handle/10665/376944/9789240094000-eng.pdf?sequence=1

[12] https://iris.who.int/bitstream/handle/10665/376944/9789240094000-eng.pdf?sequence=1

[13] https://www.who.int/publications/i/item/9789240093461

[14] https://www.gov.uk/government/publications/uk-5-year-action-plan-for-antimicrobial-resistance-2024-to-2029/confronting-antimicrobial-resistance-2024-to-2029

[15] https://www.england.nhs.uk/long-read/antimicrobial-products-subscription-model-guidance-on-commercial-arrangements/

[16] https://www.ft.com/content/f64170fe-ccd9-4854-b37a-00469c53b996

[17] https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A52023DC0190&qid=1682665765572

[18] https://www.who.int/news-room/events/detail/2024/09/26/default-calendar/un-general-assembly-high-level-meeting-on-antimicrobial-resistance-2024