FAQ

Developing a new antibiotic is time consuming, costly and, most of all, not guaranteed to succeed. As such, it is a risky endeavour for pharmaceutical companies to partake in. Furthermore, with AMR on the rise, newly developed antibiotics should be preserved except for when absolutely needed. Because of these constraints, the market for them is shrinking. All of this makes the development of new antibiotics unattractive for the private sector.

A number of companies are producing antibiotics (IFPMA, 2015) (Access to Medicine Foundation, 2018), but many of these are only variations on existing antibiotics. Such ventures are a safer bet for companies to invest in because less research is needed and approvals are faster due to similarities to existing approved drugs. However, these slightly modified antibiotics only overcome resistance for a short period of time.

Discovering new antimicrobials and using them inherently poses the risk that those new drugs may develop resistance over time. Ideally, the newly discovered antimicrobials should be restricted for last resort use only, which makes the market unattractive for the private sector in terms of sales volumes.

Developing a new antibiotic can take over a decade and cost over €850 million (Drive-AB, 2018). It can generally be divided into two main phases: initial R&D development, which is done by SMEs and public institutions mostly, followed by drug development and testing, which is done by larger pharmaceutical companies. The AMR Industry Alliance reports investment of around 2 billion into AMR research across 22 companies in 2018 (AMR Industry Alliance, 2018). While a number of companies are producing antibiotics (IFPMA, 2015) (Access to Medicine Foundation, 2018), many of them are variations on existing antibiotics. While these are a safer bet for companies to invest in as less research is needed and approvals are faster due to similarities to existing approved drugs, these slightly modified antibiotics only overcome resistance for a short period of time. Research into novel antibiotic classes is very low.

As our last-resort antibiotics, such as colistin and carbapenem, lose their efficacy (CIDRAP, 2017) (Meletis, 2016) it is imperative that antibiotic R&D is prioritised so that we may have new and effective antimicrobials in time.

Taxing has been used previously to raise revenues or alter the behaviour of the public (e.g. tobacco) and it could be a solution to reducing the overall use of antibiotics. It could have the added benefit of providing a revenue stream to fund future research in antimicrobial development. However, O’Neill, in his extensive AMR review for the UK government, warns that the antibiotic tax’s impact will greatly vary depending on its context. It is therefore wiser to implement it at the national level rather than globally (AMR Review, 2016).

In the case of antibiotics, it might be more interesting to impose a tax on antibiotics only for animal-use. This would discourage their use in husbandry but would not directly increase the healthcare costs of citizens. Furthermore, it is unlikely that raising the costs of antibiotics for medicine would lead to behaviour changes from patients (AMR Review, 2016). In 2016, Belgium implemented a tax on veterinary antibiotics that began in April 2018 (KCE, 2019). This tax earns between 450,000 and 500,000 Euro annually which is then used to further fund initiatives to promote the prudent use of antibiotics. Although the tax has not been active long enough to attribute any strong reduction in usage to it, a 2019 report by KCE indicates that the tax itself may be too low to stimulate changes in behaviour (KCE, 2019).

Denmark also introduced taxes on veterinary antibiotics in 2013 which raised the tax on critically important antimicrobials such as fluoroquinolones and third- and fourth-generation cephalosporins to 11% (FAO, 2019). While the tax aimed to promote appropriate usage of antimicrobials in husbandry, the report, similar to the aforementioned Belgian case, also found little evidence of behavioural changes (FAO, 2019).

There are a number of reasons why governments are slow to react to AMR. For one, AMR is a very complex issue due to its global and multisectoral nature and simple national policy cannot have a strong effect on it. Furthermore, even if there is political will, the public has yet to seize the AMR issue wholeheartedly and demand concrete action from their governments. (Wellcome Trust Fund, 2019).

A wide array of reports on AMR have been published by a variety of sources and all call for action. Here are some of them: WHO, AMR Review, ECDC 2017, OECD 2018, World Economic Forum, ECDC 2019, OECD 2019, CDDEP 2019, EC 2017, FAO 2016, Access to Medicine Foundation 2018, Chatham House 2019.

Recommendations:

Specific steps to reduce antimicrobial demand are:

1. A massive global public awareness campaign: this is to decrease the number of patients or farmers demanding antimicrobials as well as medical doctors and veterinarians prescribing them when it is not needed. O’Neill’s review estimates that the cost of such a global campaign would be between 40 and 100 million USD per year.
2. Improve hygiene and prevent the spread of infection: hygiene is still a problem in the 21^st century and is one of the essential steps to ensure a decrease in AMR. For the developing countries the focus will be on expanding access to clean water and sanitation. For countries that have already reached that stage the focus will instead be on hospital sanitation to prevent the rise of superbugs.
3. Reduce unnecessary use of antimicrobials in agriculture and their dissemination into the environment: here the focus is on stopping non-therapeutic use of antibiotics. In other words, ending usage to improve growth or for preventative use. Three steps are proposed for this action
   • Follow the 10-year targets proposed in the AMR Review 2015
   • Restrict the use of certain highly-critical antibiotics
   • Improve transparency of the food sector when it concerns antibiotic use
4. Improve global surveillance of drug resistance and antimicrobial consumption in humans and animals: surveillance is one of the cornerstones of infectious disease management, however it is under-utilised when it comes to AMR. After the Ebola crisis, several countries and organisations have begun to invest in this area which has created a model for other countries to build on. (Global Health Security Agenda for the US, Fleming Fund for the UK, and the Global AMR Surveillance System for the World Health Organisation). Cooperation between governments as well as open, transparent data sharing is critical for improving global surveillance.
5. Promote new, rapid diagnostics to cut unnecessary use of antibiotics: Access to rapid and trustworthy diagnostic tools would limit the occurrences of wrongly prescribed antimicrobials and significantly reduce AMR. For O’Neill et al., it is rich countries that must lead the way here; he believes that by 2020 it should become mandatory for antibiotic prescription to follow informed testing. This would have the added benefit of providing incentives to diagnostic developers.
6. Promote development and use of vaccines and alternatives: vaccines are already available today and can significantly reduce the occurrence of infections, thereby reducing the stress on antimicrobials. There are 4 main categories of vaccines relevant to AMR that we need to develop and these target: ‘community-acquired infections’ (prevent bacterial infections acquired by the general population); ‘hospital-acquired infections’ (prevent bacterial infections often developed in hospital contexts); viral infections (even though these do not require antibiotics, they are often misdiagnosed as such); and infections from animals (AMR Review 2016). However, other alternatives such as bacteriophages are also being developed. Actions needed are:
   • Use existing vaccines and alternatives more widely in humans and animals
   • Renew impetus for early-stage research
   • Sustain a viable market for vaccines and alternatives.

Examples of needed vaccines for community and hospital-acquired infections (AMR Review 2016):

• Universal pneumococcal conjugate vaccine (against Streptococcus pneumoniae)
• A vaccine against certain coli strains (no vaccines at the moment and only 2 are in the early stages of clinical development)
• There are currently no licensed vaccines for bacteria considered by the US Centers for Disease Control and Prevention (CDC) to be our most urgent AMR threats – carbapenemase-producing bacteria (including Klebsiella (no vaccine candidates), E. coli (2 vaccine candidates in Phase I trials)), drug-resistant gonorrhoea (no vaccine candidates), and difficile (vaccines in clinical development).

Steps to increase the number of effective antimicrobial drugs to fight infections resistant to existing medicines

1. Establish a Global Innovation Fund for early-stage and non-commercial research: The review proposes establishing a Global Innovation Fund endowed with up to 2 billion USD over 5 years by bringing together different initiatives of similar function that have emerged over recent years. (US via the Biomedical Advanced Research and Development Authority and Europe via the Innovative Medicines Initiative and Joint Programming Initiative for AMR programmes)
2. Better incentives to promote investment for new drugs and improving existing ones: The antibiotic market is not very attractive to large pharmaceutical companies and the reduction of antibiotic usage necessary to tackle AMR will only compound the problem. Governments must play their part by, for example, resorting to national purchasing and distribution systems. The review proposes a “system of market entry rewards of around one billion USD per drug for effective treatments.”

A global coalition for action on AMR is needed for these steps to succeed. The review states that it could be done via the G20 and the UN.

Source: AMR Review 2016