It was 2013 when Sally Davies, then England’s chief medical officer, realised a deadly problem was in the making.
Antimicrobial resistance (AMR) — when infection-causing microbes become immune to the medicines used to combat them — was worsening, her advisers told her. Pipelines for drugs that could defeat such “superbugs” were drying up, they said.
“Part of my role was to publish an annual report on the state of the nation’s health. I decided to do one on infection because that goes from community to hospitals and impacts all of us,” she says. “And, actually, I thought it would be very straightforward. But what I saw was the data getting worse year on year,” Dame Sally recalls. “And no one making a move to make it a global issue.”
According to a 2018 study published in the journal Frontiers of Immunology, AMR kills 700,000 people worldwide a year, a figure that is expected to rise to 10m by 2050 — or the number of people who die of cancer every year at present.
Now the UK’s special envoy on antimicrobial resistance, Dame Sally has since worked hard to do just that. Although the world’s attention is currently focused elsewhere — on the new coronavirus, and its drastic consequences for public health, everyday life and the economy — Dame Sally points out that there are “quite a lot of parallels” between AMR and the pandemic.
“People discount the future,” she says. “They worry about the moment, and they try to sort out the moment and the near-term.” It is hard, she says, for politicians to find the time to think about — and the money to address — anything but the most immediate eventualities.
That bias can prove costly. As the threat from coronavirus slowly became clearer, some countries — South Korea, Denmark, Taiwan, among others — responded more quickly and decisively than others. They now appear to have been better able to withstand the pandemic, and have managed either to cope without lockdowns or to lift them early.
Like coronavirus, AMR is also a global threat — arguably a still greater one, with commensurate benefits to be gained from early action.
The pipeline problem
AMR is rooted in the world’s decades-long over-reliance on and misuse of antibiotics and antimicrobial agents, which allow bacteria and other pathogens to evolve resistance to them. Because there is no safe means of killing the microbes responsible, the resulting infections can be fatal.
Whereas Covid-19 hits the elderly and those with pre-existing conditions hardest, AMR potentially affects the full spectrum of the population. Outbreaks of antibiotic-resistant bacteria in some hospitals have substantially increased the risks for patients.
Though it has been seven years since Dame Sally sounded her alarm, a solution has proved elusive. That, however, may be due as much to flawed economic incentives as to shortcomings in scientific research.
Thomas Cueni, director general of the International Federation of Pharmaceutical Manufacturers and Associations, says the phenomenon is “a shocking failure of the global public health system”.
“With AMR, we have a public health threat [that] could have as great, if not bigger an impact on our health, health systems and economically as Covid-19,” he explains. “We know about it, and we know what needs to be done: create a viable environment that fosters . . . research and development and ensures that the growth of resistance is sustainably managed and controlled.”
The pharmaceutical solution to AMR is to create antibiotics that are targeted at particular microbes and are to be used sparingly — otherwise the cycle of overuse and evolving resistance is likely to recur. But attempting to fill drug pipelines with such niche drugs is essentially a lossmaking business.
The case of US company Achaogen, which filed for bankruptcy last year after coming up with a drug for antibiotic-resistant microbes that was approved by US regulators, is one of many. According to Mr Cueni, the company made less than $1m in sales a year, but said it needed $40m a year over a decade in order to survive and recoup its investment.
“Companies in this field lose less money when they fail, as they can write off their research investment,” Mr Cueni says. “This has to change.”
Again, coronavirus shines a light on the AMR question. Markets have now taken a potential antiviral candidate for the new coronavirus as a bellwether, with good news boosting indices and bad dragging them.
But that drug, remdesivir, was first developed for Ebola and never approved by regulators — initially bringing little value to the company making it, Gilead. Putative AMR drugs may likewise take a long time to prove their worth.
“If someone had brought to market a Covid-19 vaccine two years ago, what would have the market said to its value? Zero,” says Kevin Outterson, a professor in intellectual property at Boston University and the executive director of Carb-X, a non-profit dedicated to funding the development of new anti-bacterial medicines.
“Timing is everything on these pandemic-type events and we need a better system that has things ready at the moment we actually need [them],” he adds. “It’s like with fire brigades: when a building is on fire you don’t then begin designing a fire truck and recruiting officers,” he says.
Companies making drugs to deal with AMR have seen a surprising failure rate, Prof Outterson says. In the past 13 months, five out of the 15 that had such drugs approved by the US Food and Drug Administration have either gone into bankruptcy or been sold for zero net value, he says.
“Go show me any other drug pipeline, oncology, or heart disease, [in which one-third] of a decade’s worth of innovation has been economically wiped out in the past year and a month,” he says.
Some models are emerging as potential game-changers. One is “delinkage”, currently being trialled for two candidate drugs in the UK. This involves paying companies not according to how much an antibiotic is actually used by the National Health Service, but according to its value to the health system.
Another possibility is to immunise people against the most common AMR organisms. “Something public health scientists are very interested in is to think of ways you can give hospital-goers a vaccine,” says Fiona Watt, executive chair of the UK’s Medical Research Council — though she acknowledges that “it sounds terrible [that you would] need to be vaccinated against going into hospital”.
Lower-tech solutions also have a part to play. Rigorous hygiene procedures have helped hospitals eliminate superbug outbreaks. Dame Sally points out that some of the lessons from coronavirus — about the benefits of handwashing, or being mindful of others when coughing — could also be valuable.
Perhaps the most important lesson is the need to be ready for the worst. Prof Watt points to the outbreak of Sars and Mers a decade ago. Policymakers and others recognised the danger at the time, she says, but “there [was] an element of ‘‘oh well, it didn’t affect many people in our country, we could go on’.”
Such complacency is no longer an option. “I’m sure this experience is a wake-up call for everybody that we have to be better prepared,” Prof Watt says.
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