Forging collaborative pathways to sustain antimicrobial innovation amid the AMR crisis

Antimicrobial resistance (AMR) has reached crisis levels, posing an existential threat to global health and economic stability. Current projections from the World Health Organization (WHO) estimate that by 2050, drug-resistant infections could claim 10 million lives annually and incur economic costs surpassing US$1 trillion. The steady rise of AMR is largely due to overuse and misuse of antibiotics, lack of novel antibiotics, and gaps in research targeting the most resistant and dangerous pathogens. This brief highlights the urgent need for targeted R&D efforts in AMR, focusing on neglected Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. These pathogens, responsible for some of the most lethal hospital-acquired infections, are often left out of R&D priorities due to their complex biology and high resistance potential. This brief also discusses funding disparities, pipeline bottlenecks, and calls for reinforced public-private partnerships (PPPs) and innovative non-traditional funding mechanisms to revitalise R&D to tackle AMR.

While AMR research has gained traction, a critical gap remains in the focus on Gram-negative bacteria, a group notorious for its resistance mechanisms and frequent occurrence in healthcare settings. Unlike Gram-positive bacteria, Gram-negative pathogens possess an additional protective membrane, making them more challenging to treat and more resilient against existing antibiotics. Among these, Pseudomonas aeruginosa and Acinetobacter baumannii have been classified by WHO as “priority pathogens” due to their prevalence and ability to resist last-resort antibiotics. Despite this, recent data from the Global AMR R&D Hub reveals that of the 12 new antibiotics currently under development specifically targeting Gram-negative bacteria, most are in the early stages and face uncertain futures due to limited funding and extensive clinical trial costs. Furthermore, many existing AMR research programs focus on Gram-positive pathogens like Staphylococcus aureus, which, although significant, already receive more attention and resources. Neglecting Gram-negative bacteria in R&D efforts leaves a substantial gap in the fight against AMR, with some strains becoming nearly untreatable in hospital environments. The Pew Charitable Trusts' pipeline review indicates that over 70% of antibiotics currently in development have limited efficacy against Gram-negative bacteria, highlighting a pressing need to realign R&D priorities.

The funding landscape for AMR reflects these gaps. Organisations like Wellcome and CARB-X have made commendable strides in supporting AMR research, yet data show limited allocations for projects targeting Gram-negative bacteria. According to the Wellcome Trust’s recent reports, the allocation for Gram-negative pathogen research accounts for only about 15% of their overall AMR funding. To address this shortfall, dedicated funding pools, risk-sharing mechanisms, and conditional grants are essential for ensuring these pathogens receive the attention they demand.

The development pipeline for new antibiotics and other antimicrobial agents is currently insufficient to address the escalating challenge of AMR. The WHO has highlighted that the existing pipeline lacks the necessary innovation and volume to tackle resistant pathogens effectively. As of December 31, 2023, the WHO reported 97 antibacterial agents in clinical development targeting drug-resistant infections caused by priority pathogens. This includes 57 antibiotics and 40 non-traditional antibacterial agents. In 2024, WHO reported that despite this activity, the pipeline remains insufficient to address the escalating challenge of AMR, with significant gaps in innovation and volume necessary to effectively tackle resistant pathogens.

Developing new antimicrobials is a complex, lengthy, and costly process, often spanning over a decade with substantial financial investment. The high failure rates and limited financial returns have led many pharmaceutical companies to deprioritise antibiotic R&D, resulting in a sparse pipeline. The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) has emphasised the need for a dynamic and sustainable innovation ecosystem to enable R&D for new antibiotics.

Initiatives to strengthen the AMR R&D pipeline

Key global initiatives have been established to address the deficiencies in the AMR R&D pipeline:

• CARB-X: The Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) launched in 2016 is a global nonprofit partnership focused on supporting the development of new antibacterial products. It funds early-stage research to accelerate the development of innovative therapeutics, diagnostics, and vaccines.
• AMR Action Fund: Launched in 2020, this $1 billion initiative aims to bring 2 to 4 new antibiotics to patients by 2030 by investing in smaller biotech companies developing promising antibacterial treatments.
• PACE Initiative: The Partnership for Accelerating Clinical Trials (PACE) focuses on supporting R&D in the preclinical space to strengthen the pipeline and increase confidence in tackling AMR in the long term.

Recent developments

In September 2024, F2G, an antifungal drug developer, raised $100 million to fund the late-stage trial of its lead drug, Olorofim, designed to treat drug-resistant invasive fungal infections. This funding highlights the ongoing efforts to enhance the AMR R&D pipeline.

In June 2024, Lilly announced a collaboration with OpenAI to leverage generative AI in developing antimicrobials for drug-resistant bacteria, showcasing the integration of advanced technologies in AMR R&D.

In October 2024, WHO, in partnership with the Global AMR R&D Hub, released a report detailing progress on incentivising the development of new antibacterial treatments, emphasising the urgent need for innovative strategies to enhance research and preserve access to essential antibiotics.

Addressing the AMR crisis requires sustained investment, international collaboration, and innovative approaches to revitalise the R&D pipeline and ensure the development of effective antimicrobial agents.

Dr Sabastine Wakdok, Director of Research, Impact Global Health

One of the greatest challenges in AMR research is attracting sustained funding for antibiotic development, which yields minimal returns compared to other pharmaceuticals due to antibiotics' “low-volume, high-value” nature. In recent years, however, non-traditional incentive models have gained traction with varying degrees of success. Models such as milestone-based funding, market entry rewards, and subscription-based payment systems have emerged as potential solutions. These initiatives aim to alleviate the financial risks associated with antibiotic development by offering guaranteed payments, subsidies, or market exclusivity for successful products.

The UK’s National Health Service (NHS) is piloting a subscription model that compensates pharmaceutical companies based on the societal value of antibiotics rather than on sales volume. Initial results from this model are promising; early assessments indicate improved interest from companies that might otherwise not pursue AMR R&D due to low profitability. Another innovative model, the AMR Action Fund, has committed over $1 billion toward advancing late-stage antibiotic candidates through collaboration with multiple stakeholders, including pharmaceutical companies and public health organisations. However, this fund primarily focuses on later-stage developments, leaving early-stage research at risk of underfunding.

Despite these advances, funding remains insufficient to address the complexities of AMR. The Global AMR Innovation Fund, a collaborative effort backed by the UK government, G7 countries, and philanthropic organisations, has seen only a modest increase in annual funding allocations. Current projections from Wellcome suggest that annual investments in AMR R&D need to exceed $1 billion to maintain a viable antibiotic pipeline, yet global contributions fall short. While the AMR Action Fund represents progress, its scope is limited, emphasising the need for a broader range of initiatives across the R&D spectrum, especially for early-stage projects that target neglected Gram-negative bacteria.

The G7 and G20 have shown commitment through declarations and limited funding initiatives, yet more consistent and substantial backing is required to sustain momentum. Philanthropic organisations, notably the Bill & Melinda Gates Foundation, have also played significant roles, funding efforts to advance non-traditional models and support neglected AMR targets. Data from the past five years indicate a 20% increase in philanthropic funding for AMR: however, without matching commitments from the public sector and the pharmaceutical industry, these efforts risk becoming isolated rather than transformative.

Public-private partnerships (PPPs) have demonstrated potential in addressing the gaps within AMR R&D by aligning the strengths of both the public and private sectors. Successful partnerships, such as those established by CARB-X and the Global Antibiotic Research and Development Partnership (GARDP), have made strides in advancing antibiotic candidates into clinical trials. CARB-X, which focuses on early-stage antibiotic development, has provided grants for projects that might otherwise have stalled. GARDP, meanwhile, has collaborated with both public and private entities to develop new treatments and bring them closer to market readiness. These partnerships show that when public and private interests align, it is possible to overcome high development costs and lengthy timelines.

Despite these successes, several barriers hinder the full potential of PPPs. For instance, intellectual property (IP) rights remain contentious, as private companies often hesitate to share IP without assurances of financial return or exclusivity. Furthermore, regulatory inconsistencies across countries can stall progress, making it challenging for PPPs to operate seamlessly on a global scale. A key recommendation for enhancing PPPs in AMR is to standardise regulatory processes across partner countries and establish clearer guidelines for IP sharing and risk pooling.

Diversifying the funding sources within PPPs is also necessary. Current PPPs often rely heavily on public or philanthropic funding, leaving them vulnerable to political and economic shifts. Introducing private-sector incentives, such as tax benefits and risk-sharing agreements, could encourage greater private investment. By establishing centralised hubs for PPPs focused on AMR, stakeholders could facilitate coordination, streamline IP negotiations, and ensure a balanced distribution of resources to address both Gram-positive and Gram-negative pathogens.

Given the challenges and potential solutions outlined above, the following policy actions are recommended to create a sustainable and effective approach to AMR R&D:

1. Increase targeted funding for neglected pathogens: Governments and funding agencies should create dedicated funding pools for research targeting Gram-negative bacteria. By prioritising high-need pathogens, these investments can close critical gaps in the AMR pipeline and incentivise projects that otherwise lack financial support.
2. Expand and diversify incentive models: Governments, in coordination with the G7 and G20, should increase support for non-traditional funding models, including subscription-based payment systems, market entry rewards, and patent extensions. A global AMR fund should support these incentives and provide sustained financial backing for both early—and late-stage antibiotic candidates.
3. Leverage political will and enhance global coordination: The G7 and G20 countries should enhance transparency in AMR funding commitments, establishing a standardised global fund for tracking and allocating resources. Political support is crucial for ensuring sustained progress, and clear accountability can encourage nations to meet funding goals.
4. Strengthen and diversify PPP frameworks: To make PPPs more effective, governments and international organisations should establish centralised hubs to support AMR-focused PPPs, providing standardised regulatory processes and resources for managing IP and risk-sharing agreements. Tax incentives for companies investing in neglected pathogens could further drive private investment, diversifying the funding landscape.

The threat of antimicrobial resistance is urgent and multifaceted and requires a global, coordinated response. Current efforts, while promising, fall short of what is required to prevent AMR from escalating into a full-blown crisis. Addressing the specific gaps in research for Gram-negative bacteria, alongside bolstering funding mechanisms and non-traditional incentives, is essential for reinvigorating AMR R&D. Public-private partnerships, properly structured and backed by political will, can bridge resource gaps and accelerate progress. However, for AMR R&D to truly succeed, sustainable and increased funding is crucial, as is the political commitment of G7, G20, and other stakeholders. A collaborative, data-driven approach will not only bring life-saving antimicrobials to market but also fortify the global health system against future resistance threats.