It’s difficult to believe that penicillin, perhaps the most well-known antibiotic, was first used in only 1928 – less than 100 years ago. This revolutionised medicine, saving millions of lives. Yet since that time, many infectious diseases have become so skilled at evading the power of these essential medicines that antimicrobial resistance (AMR) is now an urgent, global, health crisis.
With one in five bacterial infections1 already resistant to antibiotics, and this figure set to rise, governments and the healthcare sector need to urgently, and collectively, act now. AMR causes more than 700,000 deaths annually, according to WHO2, including around 35,000 across Europe3. Yet the pipeline for new antibiotic and antifungal products is dwindling, due to limited investment by large pharmaceutical companies. This is because current pricing models make it unsustainable in an environment where new antibiotic use is increasingly restricted to try to slow the emergence of AMR.
Huw Tippett, CEO, Shionogi Europe, explains: “AMR occurs naturally when bacteria, viruses, fungi and parasites change over time. It’s part of evolution. They evolve just like the human race. As we introduce new antimicrobial medicines such as antibiotics, bacteria find new ways of overwhelming them”. AMR was responsible for more than twice the number of deaths due to tuberculosis, influenza and HIV/AIDS combined in 20204 and is a very serious threat. New antibiotics are subject to strict controls restricting their use to slow the development of resistance.
However, it can cost more than $1bn5 to bring new antibiotics to market, which is a huge investment. “The market needs to incentivise that investment in research without companies needing to rely purely on large volumes of sales to recoup their outlay. It takes between 10 and 15 years to develop a new antibiotic, so we need to act now to ensure we have a sustainable supply for the future,” Tippett explains.
Former chief medical officer, Professor Dame Sally Davies, has warned that routine operations like hip replacements could become deadly within 20 years without effective antibiotics to treat any treatment-related infections. And organ transplantation would be virtually impossible. All of modern medicine, she maintains, stands on the shoulders of antibiotics. According to WHO, 10 million people globally could die from AMR each year by 2050 if urgent action isn’t taken2. AMR is growing at a faster rate than the ability to develop new antimicrobials, including antiviral and antifungal medicines as well as antibiotics.
Tippett warns: “Without innovation, we could go back to the pre-antibiotic era in the 1930s and 1940s when you could die from a minor infection after a cut. Antibiotics have made previously life-threatening diseases like pneumonia treatable.
“There are also financial costs to consider. The World Bank has estimated that by 2050, the health costs of AMR alone could be an additional $1tn.”6
AMR results in more patients in intensive care and bigger drug bills. A day in intensive care in the UK costs more than £1,5007, while prolonged hospital stays affect the productivity of both patients and caregivers. But AMR is a bigger problem in countries where there is no access to sanitation facilities that are not shared with another household, which affects more than 2 billion people.8
Creating a sustainable marketplace
Research and development for new antimicrobials is a complex and costly process. After testing, only one in 30 novel antibiotics in pre-clinical development reaches the marketplace.9 Bringing a drug to market does not ensure success, as shown by recent bankruptcies of some biotechnology companies operating in this therapeutic area. Small wonder then that insiders talk about the perils of pharmaceutical roulette.
There is also a unique factor that mitigates against pharmaceutical companies casting a speculative eye on antibiotics. The overuse of antibiotics can contribute to AMR, so new antibiotics are subject to strict controls restricting their use to slow the development of resistance.
Shionogi has been part of a pilot programme run by NHS England and the National Institute for Health and Care Excellence (NICE) which could revolutionise the way pharmaceutical companies are paid for antimicrobial medicines. The idea has been to test an innovative approach whereby companies receive a fixed annual fee for antimicrobials rather than the volume used.
“These fees are based primarily on a health technology assessment of their value to the NHS,” Tippett explains. NHS England said: “It is the first time any health system in the world has successfully assessed the value of an antimicrobial in this way.”
In another pioneering collaboration, Shionogi became the first pharmaceutical company to set up a relationship with the Swiss-based, not-for-profit body GARDP (the Global Antibiotic Research and Development Partnership). The Clinton Health Access Initiative is also involved in this programme to make antimicrobials available in low- and middle-income countries. Tippett believes global action like this is required to prevent further emergence of resistant strains of bacteria and protect all healthcare systems. “AMR knows no borders. We need to support these countries,” he says.
Shionogi’s collaborations are not restricted to healthcare providers such as the NHS and philanthropic bodies such as GARDP. It is also building relationships with companies such as the global biotech F2G, a specialist in fungal conditions.
Fungal infections are widely associated with minor conditions such as athlete’s foot, but patients with blood cancers such as leukaemia or lymphoma and compromised immune systems can develop life-threatening invasive fungal infections. According to a journal from The Lancet, there are about 6.5 million invasive fungal infections and 3.8 million deaths a year.10
There has not been a new class of antifungal medication approved since 200211, and concerns over the public health risks are growing with the emergence of increased resistance to existing treatment options. This led to the WHO publishing its 2022 list of health-threatening fungi, with the aim of driving further research and policy interventions to strengthen the global response to antifungal resistance.12
A make or break year
Actions designed to encourage new antimicrobial drug development, such as the UK’s innovative subscription payment system, are likely to be a major focus at a high-level UN General Assembly meeting in September “to set a politically defined vision to provide clear direction and accelerate the global response to AMR.”
With the 50th G7 summit in June also expected to feature AMR as a key topic, and the fourth global ministerial meeting on AMR in Saudi Arabia in November, there is no shortage of opportunities for world leaders to unite around solutions in 2024. Experts hope this focus will lead to greater acknowledgement of the crisis and decisive, collective action.
“I believe it shows that the scale of the growing AMR threat is being recognised,” says Tippett. “We need G7 governments to lead on fixing the market for infectious disease medicine to ensure we have a future with effective antibiotics. Without this, there is a very real risk that more companies will leave this critical field, which would have a devastating impact on the next generation.”
Shionogi Europe is a leader in the fight against AMR. To find out more, visit shionogi.eu
1. English surveillance programme for antimicrobial utilisation and resistance report (November 2023)
2. No Time To Wait: Securing the future from drug-resistant infections, IACG Report
3. European Centre for Disease Prevention and Control: Antimicrobial resistance surveillance in Europe 2023
4. Embracing a one health framework to fight Antimicrobial Resistance, Organisation for Economic Co-Operation and Development (OECD) report
5. Wouters OJ, McKee M, Luyten J. Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA. 2020 Mar 3;323(9):844-853
6. World Health Organisation Fact Sheet - Antimicrobial Resistance (November 2023)
7. Guest JF, Keating T, Gould D, Wigglesworth N. Modelling the annual NHS costs and outcomes attributable to healthcare-associated infections in England. BMJ Open. 2020
8. Maillard JY, Bloomfield SF, Courvalin P, Essack SY, Gandra S, Gerba CP, Rubino JR, Scott EA. Reducing antibiotic prescribing and addressing the global problem of antibiotic resistance by targeted hygiene in the home and everyday life settings: A position paper. Am J Infect Control. 2020 Sep;48(9):1090-1099
9. WHO: Lack of innovation set to undermine antibiotic performance and health gains
10. Denning, D W: Global incidence and mortality of severe fungal disease, January 2024
11. Butts A, Krysan DJ. Antifungal drug discovery: something old and something new. PLoS Pathog. 2012 Sep;8(9):e1002870
12. WHO fungal priority pathogens list to guide research, development and public health action (October 2022)
NP-EU-NP-0227 March 2024
