Almost a century after Alexander Fleming’s groundbreaking discovery of penicillin, his scientific successors are racing to save modern medicine.
Infections that used to be easy to cure with antibiotics are becoming so untreatableand a new treatment for bacterial infection is the holy grail for teams of researchers around the world.
However, severe financial challenges have left the pipeline of new antibiotics thin and fragile – and treatments are not available in many of the places where they are. the most necessary. Big pharmaceutical companies left the field in search of bigger profits elsewhere, and talented researchers opted for new jobs in more stable sectors.
The number of deaths caused by drug-resistant bacteria in 2019 was 1.27 millionand economic costs are on track Exceed $1 billion (£765 billion) by 2030. The death rate is the highest in sub-Saharan Africa, true children under five are particularly affected.
“This is a problem that really affects the whole world, rich and poor countries alike,” says Jeremy Knox, the head of infectious disease policy at Wellcome. “[But] the impact is decidedly asymmetric. People in low- and middle-income countries bear a much greater burden.”
World leaders will meet in New York this month to discuss antimicrobial resistance (AMR) at the UN General Assembly. They will consider how to convince researchers and companies that it is worth creating new replacement drugs, and how to improve access to tests and treatments.
The World Health Organization produces a annual list of drug-resistant pathogens that are of greatest concern. In June it warned there were too few antibacterial drugs to fight them in development.
“We are facing a crisis of innovation,” said Damiano de Felice, the head of external affairs at Carb-X, a nonprofit organization that aims to accelerate the development of such products. Only one new class of antibiotic has been discovered or patented since 1990, he says — a sharp decline since more than 25 were discovered between 1940 and 1979.
There are many new, promising approaches in the early stages of development, he says, “but most of the product developers in this space are very vulnerable”.
Of 112 commercial institutions identified by the WHO conducting preclinical research to develop new products against AMR, 97 had fewer than 50 employees.
Anand Anandjumar is the co-founder and CEO of Bugworks, one of the small companies working in AMR research. “We are barely 30 people,” he says, adding that the company – based in Bengaluru, India – “couldn’t be here” without the support of funders such as the Wellcome Trust, Carb-X and the Indian government.
In recent years, the few companies that have been successful in bringing new products to market “have done very poorly, financially”, says De Felice, with many going bankrupt.
That record scares off commercial investors and contributes to a brain drain out of the sector, with researchers starting to work on AMR moving to other fields after companies collapsed or funding disappeared.
“It’s really hard to make a lot of money from an antibiotic,” says Laura Piddock, scientific director at the Global Antibiotics Research and Development Partnership (GardP), which is working on new treatments.
Cheap drugs for chronic conditions like diabetes or high blood pressure can still make companies big profits because they are taken by many people for a long period of time – often a lifetime. In contrast, antibiotics are used for a short period of time to treat infections.
Piddock is optimistic that the scientific challenges of finding new chemical compounds to fight troublesome bacteria can be overcome, especially with the advent of new tools such as artificial intelligence.
The bigger challenge is translating that research into new treatments, she says. “Whether you’re big pharma or a small nonprofit like GardP, it still costs millions.”
Access even to existing medicines remains a problem in countries of all income levels, she says, with many companies marketing their medicines in fewer than 10 countries “for financial reasons”. This means patients in hospital with sepsis may not have access to antibiotics “that you and I take for granted”.
An Access to Medicine Foundation report found this year unlikely to change. By looking at five major pharmaceuticals in late-stage development for some of the “most serious drug-resistant pathogens,” researchers identified concrete commitments to register them for use in just five low- and middle-income countries.
The issue needs incentives that drive innovation, says De Felice, such as grants to support early-stage research from governments and the third sector.
It also needs incentives that draw drugs to market and guarantee companies a return on their investment, even if the antibiotics are not used but kept in reserve as a last resort for particularly serious infections.
Some of those programs already exist. In the UK, drug companies can receive a fixed annual fee for new antibiotics, regardless of how much they are used. The subscription model bases payments on how valuable the drugs are to the health system.
A similar approach is being considered in the US – although some global health campaigners fear it is too domestic in focus and will drive up the price of new antibiotics around the world, making it harder than ever for people in developing countries to get their hands on them.
Multiple countries will need to adopt similar incentives to sufficiently stimulate the market, says Piddock.
Some countries where access to drugs is more difficult may also lack vaccines and even basic water and sanitation, which can make infection more likely.
“What we need is to ensure that when we develop new innovations such as diagnostics and antibiotics that they are accessible and affordable in all countries, and for all populations within countries,” says Esmita Charani, an associate professor at the University of Cape Town and honorary professor. Reader in Infectious Diseases, AMR and Global Health at the University of Liverpool.
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Carb-X is partially funded by the Bill & Melinda Gates Foundation, which supports the Guardian’s global development journalism via theguardian.org. Read more about how the Guardian ensures its editorial independence here
