Nothing less than an entirely new model of drug development is needed if we are to create new antibiotics says Dr Peter Jackson. And it’s something NICE are finally taking seriously as they set about developing a new payment model – good news for many waiting for a UK response to antimicrobial resistance...
The UK’s status as being at the forefront of the fight against antimicrobial resistance (AMR) has been enhanced by several developments over recent months. Government directives coupled with newly announced private sector partnerships means the country is better placed than ever to lead the development of vitally needed new drugs to treat serious conditions caused by bacteria that have developed resistance to antibiotics.
AMR is a growing major health problem, which if left unchallenged, could kill more than 10 million people globally each year by 2050, and cost the worldwide economy between $60 and $100 trillion. It occurs when microbial pathogens develop resistance mechanisms to protect themselves from the effects of antibiotics. As bacteria are exposed to a particular drug, a small number of these bacteria will survive by evolving to develop resistance, then multiply – ensuring that the next generation of bacteria is even more difficult to treat.
This process means that infections which were once easily treatable can become extremely difficult to fight, resulting in everyday procedures, such as knee replacements, chemotherapy or C-sections becoming potentially life-threatening procedures.
NICE and NHS England will develop a payment model that rewards pharmaceutical companies according to the value of their medicines to the NHS, rather than by the amount of antibiotics sold
The World Health Organisation has reported rates of resistance increasing at an alarming rate, and the spread of these pathogens is not limited to countries without a strong healthcare infrastructure or good antibiotic stewardship. In August 2019, a study found that almost 50% of bacteria samples collected from public areas of London were resistant to not just one, but multiple antibiotics.
From push to PULL
Fortunately, solutions to the crisis are being developed by a variety of international organisations, from across the private and public sectors. Universities, institutions, biotech companies, and health providers are collaborating, using their combined expertise to develop innovative solutions to the challenge of AMR.
In 2014, then-PM David Cameron commissioned former Goldman Sachs economist, Lord Jim O’Neill, to draw up a review on the economic repercussions of AMR, should it be left untreated. The findings were shocking and have served as a point of reference for health professionals and policymakers the world over. The O’Neill report highlighted the urgent need for new treatments, as no new classes of drugs had been developed for over 30 years, and that the global market for research, development and commercialisation of new antibiotics was effectively broken.
Following this ‘call to arms’, in 2016 the AMR Centre was created at Alderley Park in Cheshire, assembling the necessary infrastructure, expertise, and unique partnering model, in order to bypass the gaps in the antibiotic development cycle, and address many of the issues with the antibiotic R&D market failure.
In order to further incentivise funding for increased R&D spending on new antibiotics, the Health Secretary, Matt Hancock, announced in January that the UK would be the first country in the world to trial so-called ‘PULL incentives’ which would reward antibiotic developers for their investment in creating and testing new drugs yet at the same time de-link payments from the amount of drug sold, to remove the pressure to overprescribe new treatments and hence drive more resistance.
To do this, the National Institute of Health and Care Excellence (NICE) and NHS England will develop a new payment model that rewards pharmaceutical companies according to the value of their medicines to the NHS, rather than by the amount of antibiotics sold.
Investors can see the unmet need for new antibiotics (especially as no new classes have been developed for over 30 years) but have questions on how to make a return on their investment. It is hoped that this revolutionary approach will solve the existing problems inherent within the antibiotic industry and encourage investors to provide the £100s of millions needed to fund research and development efforts to find new antibiotic therapies.
The need for collaboration
The large cost of R&D is also why collaboration is key in order to share expertise, capacity and funding, help create the new antibiotics that are so badly needed. The AMR Centre’s partnership with Shionogi, announced in July, is a great example of this.
Shionogi had developed COT-143, a novel humanized monoclonal antibody that doesn’t kill bacteria directly but is an anti-virulence drug that targets a specific region on the surface of Pseudomonas microbes that causes inflammation and prevents the immune system from acting against the infection. COT-143 has already produced encouraging results in pre-clinical studies and regulatory toxicology tests in preparation for first-in-human clinical trials.
The completion of the partnership agreement means that the AMR Centre will further progress this novel anti-virulence approach into clinical trials for patients suffering long-term lung infections by utilising our partnership network and development capability across the North-West of England.
The AMR Centre will also be responsible for manufacture of the complex active ingredient in time for Phase 1 safety studies in volunteers at the end of 2020, and will work with Shionogi on future strategies to commercialise the drug around the world once clinical trials have been successfully completed.
The AMR Centre’s international collaboration with Shionogi and the UK’s introduction of ‘PULL’ incentives are significant developments that will enable investment to accelerate the creation of new drugs and the bridge some of the gaps that often stop potentially lifesaving programs moving forward.
The UK is at the vanguard of the global AMR challenge, and while further innovation, collaboration and incentivisation is required to make the progress that is so vitally needed, it is encouraging to know we are heading in the right direction.
Dr Peter Jackson is Executive Director of The AMR Centre – a key part of the UK’s response to the global threat from antimicrobial resistance. Based at Alderley Park in the UK.