Issue No. 24: A year of research reveals concerning trends in AMR
Today marks the start of World Antimicrobial Resistance (AMR) Awareness Week. While fighting drug-resistant pathogens is a year-round commitment, this week is a special time to focus on raising awareness about superbugs, taking action to address AMR, and reflecting on the developments of the past 12 months.
There’s no shortage of developments to review. Since last year’s World AMR Awareness Week, scientists and global organizations have published key research that reveals concerning trends in antimicrobial resistance — and reinforces just how critical it is that the world acts now to stop AMR in its tracks. Here are just a few highlights.
WHO report shows the antibacterial pipeline is broken
In June, the World Health Organization released its annual report on the research and development pipeline for new antibacterials. Considering bacteria have already become resistant to many of our existing antibiotics, having a robust R&D pipeline is key to the fight against superbugs.
The good news is that the report shows a slight increase in the number of antibacterials in development, from 80 in 2021 to 97 in 2023. Fifty-seven of those are traditional antibiotics, while forty are nontraditional. The bad news is that this slight increase is not nearly enough to meet the need.
Since the WHO issued its first pipeline report in 2017, only 10 traditional antibiotics and two nontraditional antibacterial agents have been approved by the FDA — fewer than two new antibacterials per year. Of the 302 drugs approved by the FDA between 2009 and 2017, antibiotics made up the smallest share at just 5.3%.
That’s not enough to keep up with AMR’s constant adaptation and evolution. The WHO report says that drugs in the pipeline or with recent approvals are “insufficient to tackle the ever growing threat of…drug-resistant infections.”
The WHO report also raises concerns about the lack of innovation in antibiotic development. According to the report, “The WHO innovation criteria are poorly addressed by newly authorized agents…No newly approved agents show any new mechanism of action or new molecular target.” In other words, today’s new antibiotics are often slight variations of previously approved antibiotics, meaning bacteria may already be capable of evading them.
Of the 32 traditional antibiotics in development designed to combat a “drug-resistant bacterial priority pathogen,” only 12 meet the WHO’s criteria for innovation: a new chemical class, a new target, a new mode of action, or absence of known cross-resistance. And there are only four antibiotics in development to fight the highest-priority “critical” pathogens.
Taken together, the WHO report underscores the urgent need for a more robust research and development pipeline — and a suite of new antibacterials that can counteract the most dangerous drug-resistant pathogens.
Researchers say AMR will take millions of lives in the coming years
In September, a large group of researchers published a studyestimating the current global burden of antibiotic resistance and forecasting its future impact. The results, which were published in The Lancet, are concerning — to say the least.
The authors estimate that there were 4.7 million global deaths associated with antibiotic resistance in 2021. That figure includes 1.1 million deaths that were directly attributable to antibiotic resistance — which is just one kind of AMR, and doesn’t consider deaths from antifungal resistance.
Using 520 million patient records across 204 countries and territories, the authors also break down trends in antibiotic resistance mortality over the past three decades. Between 1990 and 2021, deaths from drug-resistant bacterial infections decreased by more than 50% among children under 5 years old but increased by over 80% among adults over 70 years old. Considering the aging of the global population, that’s a concerning trend — one that may lead to many more AMR-related deaths in years to come.
Indeed, the authors project that there will be 8.2 million deaths associated with and 1.9 million deaths directly attributed to antibiotic resistance each year by 2050 — nearly double the figures from 2021.
Altogether, there will be an estimated 39.1 million deaths attributable to antibiotic resistance across the globe over the next 25 years — about three deaths every minute. And perhaps most concerningly, there will be a whopping 169 million deaths associated with antibiotic resistance around the world over the same time period, according to the study.
One death, let alone 169 million, is far too many. Each one should be an even greater sign to alter course.
The economic cost of inaction
Research from the past year clearly indicates that there will be a massive human cost if the world continues down its current path. But previous research indicates there will be major economic costs as well.
A 2017 report from the World Bank estimates that, around the globe, the impacts of AMR could cause up to $3.4 trillion in gross domestic product losses annually by 2030.
The World Bank also predicts that the impact of AMR on global annual GDP over the next quarter-century could be worse than the impacts of the 2008-2009 financial crisis. According to the report, the economic impacts of AMR “would be felt during the entire simulation period (through 2050), not just for a couple of very bad years.” Low-income countries would bear the brunt of these impacts, due to “higher infectious disease prevalence and greater dependence on labor incomes in countries with lower per capita incomes.”
AMR will have a huge impact on the health system specifically. By 2050, drug-resistant pathogens could cause an additional $1 trillionin healthcare costs around the globe.
Wanted: A fundamental change in antimicrobial economics
Taken together, developments in the AMR space over the past year have only further highlighted how critical it is to make some progress in the fight against superbugs. That will require changing the economics of the antimicrobial market.
Each time someone takes an antimicrobial, the targeted pathogen has an opportunity to survive and, eventually, develop resistance. As a result, doctors prescribe antimicrobials judiciously, and often maintain novel therapies as a last resort for particularly severe infections.
That’s good for slowing antimicrobial resistance. But the unpredictable sales volumes are difficult for antimicrobial innovators, who typically commit over $1 billion and up to 15 years to develop a single drug.
Without a viable opportunity to recoup their investments, many companies face difficulty staying afloat. Even the most innovative breakthroughs targeting the WHO’s priority pathogens may never get to patients — or prevent millions of future deaths — under the status quo. The current economics simply don’t line up.
The solution? The right mix of “push” and “pull” incentives.
“Push” incentives reduce the costs of drug development for innovative companies. For example, the government and non-profit organizations often devote funding to antimicrobial research.
“Pull” incentives, meanwhile, reward the successful development of antimicrobials. Fortunately, there are pull incentive mechanisms under discussion around the globe, including a bipartisan proposal being considered in Congress.
Under the bipartisan PASTEUR Act, companies that successfully develop an innovative antimicrobial would have the opportunity to enter into a contract with the government for access to the antimicrobial, thereby doing away with the current volume-based sales model. Rather than being dependent on the volume of doses sold, the mechanism would be centered around the value of the novel product to public health.
In turn, PASTEUR would allow antimicrobial developers to earn back their investments, regardless of how much or little their product is used. The policy proposal would go a long way toward fixing the broken antimicrobial pipeline and averting the massive human toll of AMR that researchers sounded alarms about this year.
This World AMR Awareness Week, it’s time to advocate for solutions that will fight AMR and save lives.
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