Drug-resistant superbugs pose a serious threat to humanity. In 2019, 4.95mn deaths globally were associated with bacterial resistance, and they may cause 10mn deaths annually and around 6.9mn extra days in hospitals by 2050. Antimicrobial resistance, or AMR, occurs because bacteria and other microbes can evolve to outsmart the tools that we use to fight them, such as antibiotics. Drug-resistant infections weigh on the lives of patients, as well as the health systems that care for them and the wider economy.
Yet innovations that could slow the march of AMR are few. “The pipeline has become thinner, not because we can’t make new drugs but because there’s no investment to make new drugs,” says Henry Skinner, Chief Executive of the AMR Action Fund, an initiative that aims to support the development of two to four novel antibiotics by 2030. “The market is substantially broken.”
The way drug development is incentivised doesn’t work with antibiotics. Bringing any medical breakthrough from invention to market costs pharmaceutical companies billions of dollars, which can usually be recouped through sales over time. This model works well in other areas such as oncology and specialty medicines. However, an important aspect of AMR control is curbing the overuse of antibiotics, which hastens the development of resistance. Rightly, new antibiotics are therefore used sparingly, and so struggle to break even, let alone turn a profit.
The spate of bankruptcies among companies attempting to develop new antibiotics, even when they have promising results, highlights the gravity of the issue. “It’s a societal problem and a patient-level problem,” says Len Friedland, who leads scientific affairs and public health in the vaccines division of GSK, one of the few large pharmaceutical companies that remains active in the space. When working as a paediatrician in hospitals in the US, Friedland remembers caring for children dealing with complex health needs that were compounded by drug-resistant infections. “The children are so resilient, they’re doing really well – but then a multi-drug resistant infection comes along, and they are devastated. They dread this.”
Older people are disproportionately affected, owning to their weaker immune system, accounting for two thirds of AMR-related deaths. 'We need to have ways to prevent these infections to start with,” says Friedland, “including through increasing uptake of existing vaccines to prevent disease and reduce demand for antibiotics.”
Slowing the spread through vaccination
AMR can’t be stopped, but it can be slowed down. Every infection provides microbes with new opportunities to mutate, so strategies to slow the spread of diseases – such as improved sanitation and vaccination – are key. Vaccines can be powerful countermeasures against superbugs. For instance, a new typhoid shot successfully curtailed an outbreak of a dangerous drug-resistant strain among children in Pakistan.
Despite their potential to tackle drug-resistant pathogens, few vaccines are being developed for this purpose. “One of the problems that developers face is that AMR infections often have very high fatality rates, but – for now – are only a small proportion of overall infections. This makes AMR-specific vaccines a smaller market compared to diseases that affect many people,” says William Hausdorff, Lead, Vaccines Public Health Value Proposition at PATH’s Center for Vaccine Innovation and Access. “In particular, the commercial incentive to develop vaccines against such diseases is limited because the added value of slowing AMR is not considered in traditional vaccine assessment frameworks. ‘If I make a vaccine against AMR pathogen, are you going to use it, prioritise it, pay for it?’,” says Hausdorff.
“We’ve seen amazing innovations in recent years, which have transformed vaccine science,” says Friedland. But to make the most of this potential, he notes, regulators and others must encourage innovative approaches to the development and licensing of vaccines targeting AMR-related pathogens. Encouragingly, the role of vaccines as important tools against AMR is gaining more recognition, says Hausdorff. The World Health Organization is developing a new approach for valuing AMR-relevant vaccines that aims to capture the broad benefits of averting infection in the first place.
Reframing the value of novel antibiotics
Some countries are already adopting new approaches to valuing antibiotics. The UK government recently launched a subscription model that proposes to pay up to £20mn a year for the most efficacious novel antibiotics targeting the highest priority resistant pathogens. The aim is to provide a stable incentive to those investing in this high-risk space, encouraging much-needed innovation while also fostering responsible stewardship of antibiotics. Importantly, the value assessment framework underpinning this model captures the wider benefits of novel antibiotics, such as enabling chemotherapy and major surgery to go ahead.
Similar models are under consideration elsewhere. In the US, the proposed Pasteur Act would introduce a subscription-style payment model for novel antibiotics. In Canada, an expert panel recommended a subscription model that would pay C$14.5mn–C$18mn per year for access to new antibiotics. In the EU, new legislation proposes a transferable exclusivity voucher for priority novel antimicrobials, which would reward innovators with extension of data protection for other products.
These initiatives are important to address the growing threat of antimicrobial resistance. The global community needs to continue working together to find solutions that mitigate the AMR threat. Organisations such as CARB-X, AMR Action Fund, GARDP, One Health Trust and the Fleming Fund are making great progress on advancing the science of tackling AMR and highlighting the urgent need for policy changes. The pay-off for these efforts will be immense.
As many experts have warned, AMR could turn back the clock on a century of medical advances, making it extremely risky to perform many life-saving procedures that are taken for granted today. There is still time to change course before it’s too late. The UN High-Level Meeting on AMR in 2024 offers an opportunity for government- and non-government stakeholders alike to commit to clear targets and actionable steps to get ahead of AMR once and for all.
