Time for antimicrobial action stations

When it comes to antimicrobial resistance the time for talk is over says Dr Peter Jackson, what we need now is decisive action. Here he discusses how we can deal with one of the greatest threats to public health today

The rising tide of antimicrobial resistance (AMR) has been creeping up on world health for some time. Last year there were an estimated 50,000 deaths from drug-resistant infections in the US and EU, and over 700,000 deaths globally – figures that are set to rise.

At the recent launch of the AMR Centre in Alderley Park, Cheshire, the new UK centre of excellence set up to accelerate the development of new antibiotics, Lord Jim O’Neill said that the UK government had ‘lost focus’ on the challenge.

This comment came 18 months after his review into AMR, which predicted that by 2050 antibiotic resistance will account for over 10 million deaths per year worldwide. If no new antibiotics are developed, the impact on the global economy will be 100 trillion dollars by the same year.

The Review outlined a series of recommendations to help tackle the crisis that have become known as the ‘Ten Commandments’. Among these were suggested measures to increase the number of effective antimicrobial drugs to defeat infections that have become resistant.

There have been no new classes of antibiotics introduced, effective against the most serious Gram-negative infections, in 55 years

There are already warning signs that the future pipeline of new treatments is in danger. Antibiotic patent applications worldwide dropped by over a half from 2004 to 2013 and there are fewer new drugs emerging from clinical trials, with only two new molecular entities approved by US regulators between 2008 and 2012, down from 16 in the early 1980s.

Most alarmingly, there have been no new classes of antibiotics introduced, effective against the most serious Gram-negative infections, in 55 years.

A centre of excellence The AMR Centre has been established as a key part of the UK’s effort to take these recommendations forward and ensure that new drugs can be developed and brought to market as efficiently as possible.

It will help in the global AMR effort by providing companies with practical support, such as scientists, labs, in-vivo capability and clinical trial project management. The centre is a public-private partnership and does not have its own discovery department, but works closely with institutes, biotech companies and pharma to co-develop their programmes as fast as possible into patients by providing funding, expertise and assistance with pre-clinical and early clinical development.

The AMR Centre does not need capital investment and already has excellent facilities at its disposal thanks to its location. By leveraging the infrastructure at Alderley Park and across its partner network, it can ensure that all funding goes into progressing new antibiotics projects for patients, not creating new buildings or facilities.

The centre is now fully up and running and has announced three international co-development programmes with biotech companies since July, with over 25 scientists now working on these in its facilities at Alderley Park. Not only is this rebuilding the capability gap in the UK, it is training the next generation of researchers in the translation of antibiotics from pre-clinical testing to clinical trials.

Funding the pipeline The main issue with antibiotic drug development is the perceived low commercial value and many big pharmaceutical companies have pulled out of antibiotics research due to negative returns on investment. Mobilising public funding and ensuring that greater financial resources are available for the fight against AMR is therefore fundamental.

The good news is that there are numerous early stage drug development programmes in universities and institutes worldwide. These are only limited in what they can achieve by the amount of funding available. The UK Government must provide further funding to accelerate a new generation of antibiotics here in the UK by stepping up the level of investment in AMR as a core part of its Industrial R&D Strategy.

Despite the re-emergence of biotechs focused on AMR, for real change big pharma must also return to the antibiotics sector

Funding initiatives launched in the past 12 months, such as CARB-X, ENABLE and GARD-P, are providing around $600m for pre-clinical to clinical translation of new treatments and diagnostics, mainly in grant support to smaller biotechs. Known as ‘push’ incentives, these are designed to encourage companies with new science to develop products targeting AMR, and are starting to transform the early new product pipeline.

While $600m of new funding is to be greatly welcomed, it is calculated that to get one new drug from discovery to commercialisation requires over $700m and takes at least 14 years. And because we need more than one new treatment, it is clear that yet more needs to be done.

Despite the re-emergence of biotechs focused on AMR, for real change big pharma must also return to the antibiotics sector. ‘Pull’ incentives are being proposed in the form of financial rewards paid to drug developers for new products targeted on the critical gaps in the market. ‘Market Entry Rewards’ will be a key part of the global response to AMR and will help to improve the commercial attractiveness of the most needed types of antibiotics.

Greater collaboration As we enter 2018, it is more important than ever to move the AMR agenda forward from policy to action and the AMR Centre will be a core part of this. Great progress has been made in the past year on reinvesting in a new pipeline of treatments for AMR, though more funding is still needed. Aside from financial support, the keys to success in rebuilding an antibiotics pipeline are capacity, scale and most importantly collaboration.

For true progression of the AMR agenda, national and international collaboration is essential to maximise the potential of new programmes. The AMR Centre is already working on this and has recently been part of an Innovate UK initiative to build collaborations with Chinese researchers. It has also identified exciting new opportunities in Russia with support from the Department of International Trade and the UK Embassy in Moscow.

Here in the UK, the Centre is collaborating with experts at Public Health England and at CEIDR in Liverpool ­– a joint venture between the University of Liverpool and the Liverpool School of Tropical Medicine – to accelerate new drug programmes towards clinical trials. As an alliance partner of CARB-X – the $450m transatlantic initiative backed by the Wellcome Trust and the US Government – it can also leverage millions of dollars to support SMEs.

Companies, scientists and funders across the world working together, we can accelerate the ideas of international researchers, bring together the facilities and people they need, leverage expertise across our global networks and help to mobilise hundreds of millions of dollars in funding. This approach will help build a worldwide initiative at a scale that will make a meaningful impact on the global threat from AMR.

About the AMR Centre

Established in May 2016, The AMR Centre is a key part of the UK’s response to the global threat from antimicrobial resistance. Based at Alderley Park, the AMR Centre is a joint private-public initiative to support/accelerate the development of new antibiotics and diagnostics through a fully integrated development capability.

 

Author Dr Peter Jackson, Executive Director of the AMR Centre, which is spearheading the UK’s response to AMR