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The threat of antimicrobial resistance

Why this issue is such a fundamental challenge


A look at some of the headline statistics on the antimicrobial resistance (AMR) issue is particularly sobering. No new classes of antibiotics have been introduced for more than 30 years and antibiotic patent applications worldwide
have dropped by over a half in the past decade.

Moreover, many innovative pharmaceutical companies have pulled out of antibiotics research due to negative returns on investment in R&D and the low commercial value placed on antibiotic drugs compared to more lucrative sectors such as cardiovascular disease and cancer.

And while the pipeline of new drugs has slowly dwindled, resistance has been on the rise.

A study recently reported in The Lancet Infectious Diseases found that antibiotics are now failing to work in a fifth of patients who suffer an infection after hospital surgery.

This global research, looking at 13,000 patients across 66 countries, found that over 12% of those undergoing procedures developed a post-operative surgical site infection (SSI).

Of these, 22% of cases were resistant to commonly-prescribed antibiotics, with drug resistance rates varying from over 16% in more developed countries to 36% in less developed regions.

The farming industry is also playing a big part in the problem, with investigative journalists uncovering the story that thousands of tonnes of the antibiotic colistin (polymyxin E) were being fed routinely to chickens in India as a growth promoter.

Colistin is considered the last line of defence against multidrug-resistant organisms and using it as an animal feed supplement is unacceptable and is already banned in China and Europe.

Yet colistin resistance is already here and spreading worldwide. Two years ago, researchers reported the emergence of plasmid-mediated colistin resistance (MCR) in isolated E.coli strains in China. The MCR mutations found so far (MCR-1, 2 and 3) are on plasmids, sections of DNA that can be transferred from one organism to another, opening the door to widespread colistin resistance across multiple bacterium types. By January 2018, the US Centers for Disease Control and Prevention had reported 29 cases of MCR resistance identified across 15 states of the USA.

News of rising resistant infections and the abuse of colistin in farming shows why we need to redouble our efforts to find new ways to treat drug-resistant infections.

Lord Jim O’Neill’s Report on AMR two years ago, supported by the UK Government and the Wellcome Trust, was an important catalyst for action. Alongside this, there have been equally important initiatives by the World Health Organization (WHO), the European Union and the US Government, as well as an unprecedented global declaration on AMR at the United Nations General Assembly in 2016.

A critical part of the challenge is to produce a new generation of therapeutics, preventatives and diagnostics to combat the rise and spread of multi-drug resistant organisms.

While a new army of smaller biotechs is focusing on AMR innovation, to truly drive research forward and strengthen the dwindling global pipeline, big pharma must be encouraged to remain in - and return to - the antibiotics sector.

In the past 12 months, great progress has been made in mobilising international support for so-called PUSH incentives - providing grant support to new product developers to push their innovations through testing into clinical trials.

Funding initiatives such as CARB-X, ENABLE and GARD-P have pledged around $600m for pre-clinical to clinical translation of new treatments and diagnostics. These initiatives have been recently joined by a $165m ‘REPAIR’ fund from Novo Holdings, as an investment in companies involved in discovery and early-stage development of therapies to combat antimicrobial resistance.

This is a great start, but as highlighted in the recent expert report by DRIVE-AB, such PUSH funding needs to be increased significantly to provide a sustainable early-stage pipeline of new treatments effective against AMR.

The AMR Centre has been established as a key part of the UK’s effort to rebuild the antibiotic pipeline by working with innovative SMEs to ensure that new drugs can be developed and brought to market as quickly and efficiently as possible.

Alongside other sources of PUSH grants, the AMR Centre works in partnership with institutes, biotech companies and pharma to co-develop their programmes as fast as possible by providing funding, expertise and practical assistance with preclinical and early clinical development, leveraging the world-class R&D infrastructure at Alderley Park and across the wider support network in the UK. The Centre has announced its first three international co-development programmes with biotech companies since opening its labs in July 2017 and has more to come in 2018.

But PUSH incentives are not enough to fix the problem with the antibiotics market.

For biotechs, pharma companies and their investors, there must be progress on the market PULL side of the equation. This means ensuring that there are clear financial rewards available to drug developers if they succeed in bringing life-saving new AMR medicines to patients.

We now need international action to establish mechanisms such as Market Entry Rewards for new drugs that might never have a commercial future, but can provide the last line of defence against the most serious resistant pathogens.

And we need healthcare payers to recognise the true value of innovative antibiotics to the healthcare system. After all, so many of today’s life-saving healthcare advances, from cancer chemotherapy to heart surgery, rely on effective antibiotics being available to prevent infections in patients.

Microbes will continue to evolve to become resistant to new treatments in time, so our research will by necessity be never-ending. For the ‘biotech army’ to be truly successful, we also need to have big pharma fully on board and incentivised to provide its infrastructure and experience in bringing new antibiotics to market.

About the AMR Centre

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.

The DRIVE-AB final report is available at:

Article by
Dr Peter Jackson

is executive director of the AMR centre

19th April 2018

Article by
Dr Peter Jackson

is executive director of the AMR centre

19th April 2018

From: Research



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