Staying ahead of antimicrobial resistance

Without action, by 2050 more than 10 million people per year will die as a result of antimicrobial resistance (AMR). Preventing this outcome, however, is not just a matter of developing new antibiotics. According to Gareth Morgan, senior vice president and head of global portfolio management and antimicrobial resistance policy at Shionogi, a Japanese pharmaceutical company, “Above all, it is a matter of addressing problems related to awareness and economics.”

“When it comes to infectious diseases, everybody knows about COVID-19, but very few know and care about AMR. There’s a big awareness problem,” says Morgan.

Antimicrobial resistance is the process where bacteria, fungi, viruses, and parasites evolve and become capable of surviving the medicines developed to fight them. Scientists have known about antibiotic resistance since Alexander Fleming discovered penicillin in 1928, but for a long time they were able to keep ahead of new resistance mechanisms with new antibiotics. It was not until the early 2000s when physicians observed increased resistance to last-resort antibiotics, that scientists and medical professionals began to take action.

Initial measures to combat AMR included support for academia and pharmaceutical companies for the early stages of new antibiotic development, often referred to as push incentives, as well as controlling the use of antibiotics through stewardship programmes. For example, prescription of some antibiotics has been limited to only the most desperate cases of infection where all other antibiotics have failed.

While stewardship measures are vital to prolonging the useful life of antibiotics, they have disrupted the normal functioning of the pharmaceutical market. “We have a situation where stewardship, which we all agree is essential, can drive very low use for new antibiotics,” says Morgan. “Paradoxically, it’s almost like, the better the antibiotic you develop, the lower the volume of sales you might expect.”

Disincentivized to develop new antibiotics, companies are not producing enough new drugs to stay ahead of AMR. Doctors have even resurrected colistin, an antibiotic first used in 1959 but considered too toxic and almost abandoned years ago, because it still has some activity. “It shows how desperate the world has become,” says Morgan.

Post-marketing economic incentives offer hope; for example, when revenue is delinked from the volume of sales, as in the programmes being piloted in the UK and Sweden. Meanwhile, the PASTEUR Act, a bipartisan bill providing for these economic ‘pull’ incentives, along with additional stewardship provisions, is being debated in the US.

The NHS in England is planning to pilot two drugs in its antibiotic subscription programme, one of which is a drug from Shionogi, adopting a methodology that Morgan describes as being a bit like the Netflix subscription model. “The country pays a certain amount of money every year, and the company provides as much of the antibiotic as needed.”

Sweden, on the other hand, is piloting a programme that pays for access. Since it can be expensive to launch an antibiotic Sweden pays the company to provide access, and hospitals purchase the antibiotic via their existing channels. In this model, the manufacturer gets some revenue even when only a small volume of drug is sold.

“The actions of the UK and Sweden are promising steps, but other countries need to follow,” says Morgan. While the global investment needed for these post-marketing pull incentives is considerable, it is far exceeded by the value of maintaining access to effective antibiotics. “If you effectively treat a patient, they don’t pass resistant bacteria on to others. And if you can keep a patient out of hospital or get them out of hospital quickly, you can reduce health care costs,” he explains. “There is value for individual patients and for society as a whole.”

Since the UN endorsed a global action plan on AMR in 2015, 67 countries have formulated their own action plans. “But we need more countries to move from talk to action,” says Morgan. “COVID-19 caught us by surprise, but we can’t say that about AMR, we know it’s an issue now.”