Antimicrobial resistance

Published 07-01-2026

Problem

The problem of antimicrobial resistance (AMR) is well known and considered a top global public health threat by the World Health Organisation (WHO). Future widespread AMR, in addition to failing to successfully treat infections, would render operations and cancer chemotherapy unfeasible due to the unacceptable risk of an untreatable infection. In 2021 the deaths associated with bacterial AMR were estimated to be 4·71 million and are forecasted to be 8·22 million in 2050 (GBD 2021 Antimicrobial Resistance Collaborators, 2024). In order to mitigate the number of AMR forecasted deaths, interventions should combine infection prevention, vaccination, minimisation of inappropriate antibiotic use in humans and farming, as well as research into new antibiotics.

Antimicrobial resistance

The European Commission and Member States have identified AMR as one of the top three priority health threats, with urgent need for new vaccines, diagnostics and medicines. Despite this, there is inadequate research and development for new antibiotics with low pipeline numbers. In June 2023 43 new therapeutic entity antibiotics were under development, however, only a handful met at least one of the WHO innovation criteria (i.e., absence of known cross-resistance, new binding site, mode of action and/or class) and are insufficient to tackle the problem of AMR (Council Recommendation, June 2023). In general, new antibiotics are being developed by small companies or academics not familiar with the data requirements to achieve a Marketing Authorisation. The lack of interest by big pharma is caused by the limited revenues antibiotic medicines could generate. In particular, should a new antimicrobial target a multi-drug resistance bacteria, it would be recommended for restricted use in order to reduce the risk of further development of AMR. With the added problem of scientifically demanding and burdensome clinical trials, the limited return on investment for new antibiotics is not conducive for development of such medicines.

Solutions in the EU

In addition to EU collaboration on an international level, a ‘One Health’ cross-agency task force has been established in the EU based upon the WHO ‘One Health’ initiative. The One Health High Level Expert Panel aims to provide a multi-stakeholder integrated approach to various topics affecting the health of people, animals and ecosystems, including combatting AMR.

Funding

As part of the ‘One Health’ approach for counteraction of AMR, the Europe Council noted an urgent need to develop and implement new incentives to develop new antibiotics such as revenue guarantee, lump-sum market entry rewards and milestone payments. These incentives may be financed at EU level, national level or co-financed (Council Recommendation, June 2023).

Research and development funding and collaboration through Horizon 2020 and EU4Health work programmes supports innovation of new antimicrobials. The European Commission have committed to coordinate the funding of translational research and late-stage development of AMR medical countermeasures, including clinical trials for antimicrobials.

A novel way for antibiotic reimbursement was recently piloted in Sweden, where the manufacturer was provided a guaranteed minimum annual revenue in exchange for supply of prioritised off-patent antibiotic medicinal products according to agreed quantities and timelines. This pilot was extended to new medically important antibiotics and will help to ensure patient access to novel antibiotics despite the limited market, as income would not be linked to sale volumes and would, therefore, be more predictable (Public Health Agency of Sweden, August 2024). The EU Joint Action on Antimicrobial Resistance and Healthcare-Associated Infections (EU-JAMRAI) ‘strategy for implementing multi-country incentives in Europe to stimulate antimicrobial innovation and access’ proposed that this Swedish model for revenue guarantee is extended to other Member States (EU-JAMRAI, 2021). The report also suggested that HTA assessments which include a societal value, in addition to patient value, may also be useful, as currently trialled in the UK and Norway.

Target product profiles

The European Commission has committed to assist Member States in mapping existing, upcoming and missing AMR medical countermeasures, and in defining target product profiles (TPPs) in alignment with national initiatives (Council Recommendation, June 2023). The focus is likely to be aligned with the 2017 WHO list of bacteria for which new antibiotics are urgently needed as well as any internationally agreed-on TPPs for antibiotics targeting these bacteria. These TPPs will help inform future research and development programmes.

EMA Guidance and Scientific Advice

The EMA collects data on antimicrobial consumption and resistance and supports the development of new antimicrobials, including new approaches using bacteriophages. The EMA have published a guidance on the evaluation of medicinal products for treatment of bacterial infections and an addendum for paediatric-specific clinical data requirements, as well as a guideline on the use of pharmacokinetics and pharmacodynamics in the development of antibacterial medicinal products. A concept paper on the establishment of a Guideline on the development and manufacture of human medicinal products specifically designed for phage therapy was also published by the EMA in 2023.

The EMA are implementing improved scientific advice for medicines for AMR as part of an initiative by the EMA’s Emergency Task Force (ETF) to improve scientific advice for health threats that have potential to cause public health emergencies. The ETF will bring together regulatory and clinical trial expertise to offer ‘SA-CTA’ scientific advice on the scientific aspects of clinical trials, which will be assessed by the ETF, the National Competent Authorities and the newly created group of ethics experts (Public Health Emergency Ethics Advisory Group, PHE EAG). This initiative will accelerate development of certain new antibiotics by ensuring alignment between the regulatory approval requirements and the national or ethics perspective on clinical trial applications (EMA news, November 2025). The EFT remit for providing SA-CTA in the context of AMR includes TB, gonorrhoea, new vaccines for bacterial pathogens, new antibacterial treatments in the areas of unmet need related to multidrug resistance (Annex 1 of ETF 3 year work plan, November 2025).

Clinical trials

The most recently approved novel antibiotics were developed following non-inferiority clinical trials, mainly due to the difficulty in finding and defining a patient population resistance to antibiotics. The Wellcome Trust and others are establishing antibiotic clinical trial networks in countries with higher resistance patterns, meaning that investigation of new antibiotics within superiority trials should be possible for resistant infections. With better clinical evidence, the national unit prices per antibiotic should increase (EU-JAMRAI 2021).

Transferable Exclusivity Voucher

The new Regulation within the European Commission’s upcoming ‘pharma-package’, that is currently under negotiation, includes an incentive to develop new antimicrobials. A Transferable Exclusivity Voucher (TEV) will be made available to Marketing Authorisation Holders (MAH) that develop a ‘priority antimicrobial product’ and can ensure availability to meet the patient’s needs. The voucher gives the MAH one additional year of data exclusivity, either to extend the marketing exclusivity of the priority antimicrobial itself or for any other centrally authorised product of the same or a different MAH. Give the lack of commercial return on antimicrobials, the MAH may use the TEV to extend data exclusivity on their most profitable portfolio drug or to sell the TEV to another company, potentially for a very large sum. A maximum of 10 vouchers has been set which can be provided within 15 years.

How can S-cubed help you?

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Any Questions?

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