More superbugs, fewer drugs. How can pharma companies ensure the handful of promising antimicrobials make it to the frontlines of drug resistance?

• Companies are employing a diverse range of strategies within their access and stewardship plans, but structured advance planning has not yet become standard.  

• Four of the five companies in scope – GSK, Pfizer, Innoviva and Venatorx – are initiating or conducting clinical trials involving children, signalling positive steps in moving towards closing the gap between adult and paediatric access. 

• Out of 113 low-and middle-income countries (LMICs) in scope, concrete commitments for registration were only identified in 5 – China, India, Mexico, South Africa and Thailand. Many of the remaining 108 LMICs in scope face high burdens of diseases targeted by the projects and could benefit from access to them.   

• The report identifies opportunities and recommendations for companies in focus and sets out actionable steps for peers and other global stakeholders in antimicrobial R&D to promote widespread adoption of advance access and stewardship planning.  

With a vast majority of large research-based pharmaceutical companies no longer active in antimicrobial research and development (R&D), due to lack of commercial viability, there are very few new treatments making it to market, leaving patients across the globe vulnerable to the rapid spread of antimicrobial resistance (AMR). Despite this reality, there are a handful of projects in late-stage clinical development that could help patients overcome some of the most severe and often fatal drug-resistant infections they are currently facing.   

The latest report from The Access to Medicine Foundation’s AMR Programme has tracked four such innovative, late-stage R&D projects across the pipelines of GSK, F2G, Innoviva and Venatorx (gepotidacin, olorofim, zoliflodacin and cefepime-taniborbactam, respectively) as well as Pfizer’s recently approved aztreonam-avibactam (Emblaveo®)*. Collectively, these projects could save at least 160,000** lives each year by providing much-needed medicines to treat drug-resistant gonorrhoea, urinary tract infections, intra-abdominal infections, respiratory infections and invasive fungal infections. While these diseases and syndromes affect a wide range of patients globally, women and children – especially those living in low- and middle-income countries (LMICs) – are disproportionately affected. 

 By analysing the depth and breadth of these five companies’ access and stewardship planning, specifically whether patients in low-and middle-income countries (LMICs) are being prioritised, the report identifies where efforts need to be scaled and how shortcomings can be addressed.  

Four key findings 

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 the five projects will be made available upon initial approval. 

Affordability and stewardship in LMICs are largely overlooked during planning 

Some of the companies assessed in this report are addressing affordability and stewardship. 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 for making new products affordable to patients in any LMIC could be identified in 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 companion diagnostics – were lacking across the board.

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 that directly target 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 and paediatric access and set an example of what can be done by other developers. 

Partnerships help scale efforts, but other tools to broaden access and stewardship plans can also be utilised 

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 Global Antibiotic Research and Development Partnership (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. Aside from collaborations with GARDP, SMEs actively seek partnerships directly with large 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 access and 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 and Access Plan (SAP) Development Guide in 2021. However, the report finds that the companies in scope are underutilising the recommendations in this Guide.  

What’s next? 

For sustainable solutions to take hold, it is vital that comprehensive and detailed access and stewardship plans are embedded in companies’ antimicrobial innovation, specifically strategies that target populations and countries that face the highest burden of drug resistance. To strengthen their efforts and increase their reach, companies can seek out partnerships for co-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. 

As is highlighted in this report, funders play a critical role in supporting antimicrobial R&D, but they can also help ensure qualitative access and stewardship planning will be implemented effectively throughout clinical development. By setting contractual provisions on access and stewardship funders can ensure their vast financial support translates into sustainable progress and improved global health.  

It is critical to act now and make sure the few antimicrobials are made available to patients on the frontlines of drug resistance. 

_{*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).} 

_{**This number is based on the annual number of deaths per syndrome 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 the Institute for Health Metrics and Evaluation. Note that the number of deaths due to invasive aspergillosis caused by drug resistant Aspergillosis spp. is not estimated and therefore not included.}