Guest blog | Destiny Pharma | Meeting the Challenge of AMR: Resisting Resistance!

Global challenge of AMR:

Anti-microbial resistance (AMR) is undoubtedly one of mankind’s greatest healthcare challenges. This is emphasised by the fact that this crisis is a main agenda item for the United Nations, World Health Organisation, G7 and G20. Lord O’Neill, chair of the UK Review on Antimicrobial Resistance, put the future in stark contrast in his 2016 report “Tackling drug-resistant infections globally” – if significant steps are not taken to address this issue, >10 million AMR attributable deaths per annum (more than currently caused by cancer) and a total cost to the global economy of $100 trillion by 2050 is predicted.

AMR existed long before man, the result of millions of years of microbial evolution. You don’t have to step very far back in history (c.100 years) to a pre-antibiotic era when infection was one of the primary causes of human mortality. The fortunate discovery of antibiotics heralded a rapid, instant cure of previously fatal infections and enabled the establishment of modern medicine and surgery.

Unfortunately, the honeymoon period has ended. Over-reliance on those early discovered antibiotics and the bacterial evolution of multi-antibiotic resistant strains, coupled with a poor return on investment profile for antibiotics, has led to the exodus of many large pharmaceutical companies from this area of research. This has resulted in far too few new antibiotics being approved to replace those rendered impotent by AMR.

Today, we face the prospect of moving back towards the pre-antibiotic era. There are just 50 antibiotic/antibacterial drugs currently at the clinical stage of development, of which just a handful are likely to become medicines, compared to the many thousands of drugs in clinical development to combat cancer.

Addressing AMR: Multidisciplinary strategy with funding challenge at its core

National and international AMR strategies have common themes: stewardship of existing antibiotics, limited use of antibiotics in livestock, collection of AMR epidemiology data, development and utilisation of appropriate diagnostic tests, and the promotion of innovation leading to new antibiotics and non-antibiotic antibacterial medicine platforms.

While there is consensus on what activities are needed to address AMR, the funding of such strategies still needs to be addressed. Antibiotics in general are taken over a relatively short period of time and often lead to a complete cure of an infection. Curiously however, they attract a relatively low price particularly if compared to other medicines which are taken over a much longer period of time, sometimes for the rest of the patient’s life.

The UK government’s 5- and 20-year plans to tackle AMR were announced in January 2019 and included a welcome commitment from the National Institute for Health and Care Excellence (NICE) and NHS England to explore new payment models for antimicrobials. A few examples of new payment models which reflect the societal value of new antimicrobials are being considered including market entry rewards, transferable intellectual property vouchers, add-on payments, guaranteed purchase, and hospital licenses.

Another strategy that has been suggested is a ‘play or pay’ levy on the pharmaceutical industry, many of whose profitable medicines rely on a foundation of effective antibiotics. If this can be swiftly resolved and the focus of the pharmaceutical industry applied, a pipeline of new anti-bacterial drugs can be secured.

Innovation abounds:

There are far too few large pharmaceutical companies operating in this space with the biotech industry being an engine for innovation. What little funding has been available has been directed at traditional antibiotic research and development, but there is a growing awareness that while new antibiotics are needed, the invention and development of new anti-bacterial medicine platforms is critical. Particularly those with a focus on novel mechanisms of action that are likely to both address AMR and have the ability to reduce resistance emergence – Resisting Resistance.

Such platforms would assist in stewardship of existing antibiotics, reduce AMR emergence, have potency against existing superbug strains, and be utilised in a widespread preventative manner as well as treatment of infections. This is an area that Destiny Pharma has researched and has developed such a platform, the XF drug platform (who’s novel bacterial membrane action has been shown to impede resistance development). Destiny Pharma’s lead candidate from the platform, XF-73, is currently entering Phase 2 clinical development and has been awarded fast track status by the US Food and Drug Administration (FDA) for the prevention of MRSA/Staphylococcus aureus surgical infections. Another promising area of development is that of microbiome-based treatments where ‘good’ bacteria are used to prevent or treat infections caused by pathogenic bacteria.

This blog was contributed to by Dr Bill Love, Founder and Chief Scientific Officer, Destiny Pharma