Avoiding the Antibiotics Apocalypse- Options for Action

Anti-microbial resistance (AMR) threatens to unravel the successes of modern medicine, compromising the efficacy of life-saving surgeries, chemotherapy, and infection treatment.

At BioInfect’s 2022 conference, I heard from leading researchers across the pharmaceutical industry as they delved into critical issues surrounding antimicrobial drug resistance and drug development. I left inspired to do my part in raising awareness of what could be “the next pandemic”.

As anti-microbial resistance accelerates, the burden on health systems is growing. Hospitals face increased mortality and morbidity from infectious disease, longer in-patient stays, and an overall increased cost of care.

By 2050, the UK alone stands to face a loss of 10 million lives to drug-resistant infections every year.  In the words of Professor Dame Sally Davies, Chief Medical Officer to the UK Government, we face an “antibiotics apocalypse”.

In this article we’ll explore:

• What antimicrobial resistance is
• Why anti-microbial resistance is a global threat
• Options for action – prevention, innovation and costs

What is anti-microbial resistance?

Anti-microbial drugs are used to treat infections caused by either harmful bacteria, or fungi. While antibiotics are used for bacterial infections, antifungals are used to treat fungal infections.

Anti-microbial resistance occurs when bacteria mutates or changes in a way that makes them resistant to drugs designed to treat infection. While AMR is in essence, a natural phenomenon, it has been accelerated by global overuse and misuse of antimicrobial medicine leading to what Professor Dame Sally Davies, England’s Chief Medical Officer describes as an “apocalyptic” crisis.

Over the last few decades, more than 100 forms of anti-microbial resistant bacteria have emerged, and more continue to be discovered. Once these drug-resistant bacteria take hold they can rapidly spread between hosts, cross international borders, and fuel health crises.

Why antimicrobial resistance is a global threat

Anti-microbial resistance threatens to undermine global health security and is outpacing efforts to contain it. Without further action, the World Health Organisation estimate a yearly loss of 10 million lives by 2050, with 4.5 million deaths occurring in the Asia Pacific (APAC) region.

Poor and vulnerable populations are less able to afford effective antibiotics and are most affected by AMR. By 2050, the World Bank estimate that AMR will push 28 million more people into extreme poverty.

A report from the World Health Organisation describes how in 2017, 82% of people who had tuberculosis infections globally had a multi-drug resistant strain of the infection. This means 82% of treatment courses were longer, more expensive and involved more toxic drugs. 

Meanwhile, recent research from The Lancet shows that both South Asia and sub-Saharan Africa have a high antibiotics consumption rate, and a higher rate of patient death. Both regions feature a higher prevalence of critical infections, alongside limited laboratory infrastructure to determine whether to stop, or narrow antibiotic treatment. 

Other drivers of a higher AMR burden in these regions include:

• Inappropriate use of antibiotics driven by ease of acquisition and insufficient regulation
• Poor access to second line, and third line antibiotics
• Counterfeit or substandard antibiotics that accelerate resistance
• Poor sanitation and hygiene

While AMR poses a greater threat in sub-Saharan Africa and South Asia, it remains a global health problem. Resistance is already high for many key antibiotic substances and shows no sign of slowing down while continuing to spread world-wide.

Options for action – prevention, innovation and costs

Enabling infection prevention

Infection prevention and control initiatives have been refined over the course of the pandemic and should be readily applied to AMR.

Research from The Lancet on the global burden of AMR suggests that the principles of infection prevention should come first when it comes to combating the spread of AMR.

Key initiatives for improved infection prevention include both hospital-based infection prevention and control programmes to help prevent infection acquires in health-care settings, and sustained support for community-based programmes focused on water, sanitation, and hygiene in developing countries.

Fostering innovation

Innovation is critical to fuel and enable the development of new antibiotics and vaccinations, as our current treatments lose efficacy, as well as new technologies to improve screening.

Vaccine development is an important preventative mechanism that leads to reduction of antibiotic prescribing to weaken AMR emergence.

Additionally, maintaining the development pipeline for new antibiotics is crucial to ensure we have the medications to replace those lost – this is particularly crucial post-pandemic as other endemics continue to spread.

Chikungunya fever has caused numerous epidemics across APAC, Africa, and the sub-tropical regions of the Americas, and currently lacks any appropriate anti-viral drug treatment.

Evotec are pioneering new ways to treat and potentially prevent chikungunya virus infections caused by Chikungunya fever. Evotec’s antibody was developed by Sanofi and is now at clinical trial stages after showing potential across in vitro and in vivo models.

When it comes to new technologies, University of Oxford’s Engineering and Physical Science department are leading a newly funded initiative to generate new commercially viable technologies to enable transformative innovation.

The programme is set to deliver:

• A treatment screening platform prototype to speed up the testing of new therapies
• A prototype of a point of care diagnostic device for healthcare and agriculture to limit inappropriate antibiotic usage
• Pre-clinical efficacy data to support new treatments for critical infections

Overcoming costs with push and pull initiatives

At first glance, funding new antibiotic therapies isn’t financially feasible for pharmaceutical companies.

New drugs are notoriously expensive to develop, and companies rely on high sales volumes to recoup their investments and enable a profit. However, antibiotic use is tightly restricted to prevent resistance and preserve the drug’s efficacy, making recruiting for and running clinical trials alone challenging.

Once the drug eventually reaches the market, its prescription will again be restricted as much as possible, generating lower sales volumes and diminishing returns. This situation has meant most large drug companies have discontinued antimicrobial drug research and development.

Today, push and pull initiatives that bring together regulatory, financial, and scientific organisations are helping to unravel the cost limitations involved with anti-microbial drug development and empower more companies to take action.

Push incentives are strategies that help to directly lower the cost of drug development. They involve support from public funding and other funding groups, pooled compound procurement and open access knowledge repositories.

In an interview with Nature magazine, Lloyd Pane, EVP Head of Evotec, describes how the number of new funding mechanisms is growing. He mentions groups including CARB-X, BARDA, the Global Antibiotic Research and Development Partnership, and the European Innovative Medicines Initiative as “highly committed to antibiotic discovery and development”. 

Additionally, Lloyd highlights the importance of “improving the regulatory framework to allow submissions for approval based on smaller clinical trials”. He highlights the instrumental role that regulatory bodies such as the US Food and Drug Administration, and the European Medicines Agency are playing in establishing better regulatory pathways.

Despite the prevalence of ‘push’ incentives, the situation remains critical. Lloyd explains, “since 1962, only two new classes of antibiotics have been approved. We need new classes of antibiotics, new targets, and new mechanisms of action.”

Pull incentives provide an additional route to cost efficiency and are ideally used alongside push incentives. Pull incentives disconnect return on investment from sales volume by providing alternative revenue generating benefits once the drug has reached the market.

Phil Thomson, President of Global Affairs at GlaxoSmith Kline explores the topic saying, “the current antibiotic market is dysfunctional. Whilst there are grounds for optimism scientifically with prospects of targeted medicines, new diagnostic technologies and vaccination, the commercial market is unattractive." 

Thomson describes how ‘pull incentives’ could “stimulate investment across the full product lifecycle, from discovery through development and onto the market – thereby making it attractive for biotech’s and larger companies to invest in antibacterial efforts”.

While GlaxoSmith Kline support a range of pull mechanisms they are just one company among many – for large scale change to occur, government and national health action is vital.

BioInfect’s 2022 AMR conference saw a range of speakers discuss the challenges faced in reducing anti-microbial resistance, including cost. Professor Colm Leonard, Consultant Clinical Advisor for NICE described the importance of incentives to support long-term R&D. Professor Leonard described a conceptual new approach to monetising antibiotic development through a ‘subscription type’ payment model, where companies are paid passed on their value to the NHS rather than the volumes used.

This approach could offer a way to de-link sales volume incentives from return on investment on a much larger scale and enable more organisations to turn their attention to antibiotics development.  

Can you help to prevent antimicrobial resistance?

Patients have an instrumental role to play when it comes to ensuring that antibiotics are consumed appropriately. In the US alone, 50% of people do not complete their medication courses as prescribed. Meanwhile a UK household survey reveals that 14% of patients who are prescribed antibiotics have left over medication, and a third of these individual keep the antibiotics for future use. Completing any prescribed antibiotics courses is critical to help preserve treatment efficacy, limit the chances of repeat infection, and curb antimicrobial resistance.  

Scientists across the world are leading the development of new innovative therapies to generate a critically needed next generation of antibiotic treatments, in the fight against the antibiotics apocalypse.

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