Antibiotics: will the industry saviour please stand up
pharmafile | November 24, 2014 | Feature | Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing | Antibiotics, EAA, MRC, WHO, resistance, susie lunt
The spectre of a new ‘dark ages’ for humanity where common infections begin to kill again is increasingly making itself felt in the UK, as well as globally.
This vision is being driven by reports such as the April 2014 study by the World Health Organization (WHO) that states antibiotic resistance – which occurs when bacteria change so that antibiotics no longer work in people who need them to treat infections – is causing a serious and worldwide threat to public health.
Based on data from 114 countries, the WHO report says that antibiotic resistance is not only happening “right now, in every region of the world”, but also has the potential to affect anyone, of any age, in any country.
“Without urgent, co-ordinated action by many stakeholders, the world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill,” says Dr Keiji Fukuda, WHO’s assistant director-general for health security, on the report’s release.
“Effective antibiotics have been one of the pillars allowing us to live longer, live healthier, and benefit from modern medicine,” Fukuda adds.
“Unless we take significant actions to improve efforts to prevent infections and also change how we produce, prescribe and use antibiotics, the world will lose more and more of these global public health goods and the implications will be devastating.”
As an example, the WHO highlights that resistance to the treatment of last resort for life-threatening infections caused by common intestinal bacteria Klebsiella pneumonia – carbapenem antibiotics – has spread to all regions of the world.
Also known as K. pneumonia, the bacteria is a major cause of hospital-acquired infections such as pneumonia, bloodstream infections, infections in newborn babies and intensive-care unit patients.
In some countries, because of resistance, carbapenem antibiotics do not work in more than half of people treated for K. pneumoniae infections. The report also notes that antibiotic resistance causes people to be sick for longer, increases the cost of healthcare, and increases the risk of death.
Thus, individuals with methicillin-resistant Staphylococcus aureus, or MRSA, are estimated to be 64% more likely to die than people with a non-resistant form of the infection.
Closer to home
Concerns are also growing in the UK, as flagged up in March 2013 by chief medical officer Professor Dame Sally Davies in a milestone report entitled “Infections and the rise of antimicrobial resistance” (AMR).
In this, she underlined the global threat to public health represented by the rise in drug-resistant bacteria and pointed to the need for research and development of new therapies addressing the crisis of antibiotic resistance.
The report drew support from big pharma players such as GlaxoSmithKline (GSK) and AstraZeneca, both of which acknowledged the importance of tackling the crisis of antibiotic resistance.
In a statement released that same month, AstraZeneca pointed to the need to “work with governments and regulators globally to help get these much-needed antibiotics into the hands of the medical community,” highlighting that, along with its industry partners, it was already working with governments to drive awareness of responsible antibiotic prescribing.
Dr Des Walsh, head of infections and immunity at the Medical Research Council (MRC), says that when antibiotics are not used properly over time, this may start to enable bacteria to become resistant to treatment.
“As treatment practices haven’t been globally harmonised, bacteria are slowly becoming resistant,” Walsh says. “This is having the outcome that not only are broad spectrum treatments not working as well, but also that targeted approaches to treatment are indicating greater potential to become resistant,” he adds.
Although antibacterial resistance is a relatively small problem for the UK, which does not suffer the burden of a high number of infectious diseases experienced in the developing world, it is a growing and major threat.
In 2014, the MRC also calculated that although £275 million had been spent in the UK on researching the problem since 2007, to date no effective solutions had been found.
“We therefore have an opportunity now to galvanise the research communities, pharma, and public health bodies to work together – first, to preserve what we have got, and secondly, to develop new approaches,” Walsh says.
With this in mind, the MRC is working in close partnership with a wide spectrum of organisations and public bodies in the form of a cross-council ‘war cabinet’ backed by eight government bodies, along with the Wellcome Trust.
Its goal? To understand antibiotic resistance from a holistic perspective and tackle AMR on all fronts. Announced by science minister Greg Clark in July 2014, the initiative involves all seven of the UK’s research councils.
It now co-ordinates the work of medical researchers, biologists, vets, engineers, economists, social scientists, mathematicians and even designers, in a multi-pronged approach to address all aspects of the multi-faceted problem.
“This is not just our project”, Walsh says. “It’s a shared position, so that we can understand all facets of resistance, from looking at potential pathways to uncover new treatments, to viewing how human behaviours affect this, or understanding the impact of the built and natural environment.”
A four-pronged attack
The first aim of the initiative’s resistance strategy is to understand resistance formation, and why it is spreading from one bacteria to another.
Second, attention is being focussed on accelerating therapeutics and diagnostics, such as how to help revisit old drugs with new science, and how to find new ways to treat bacteria, for example by enhancing our own immune systems.
The aim is to diagnose bacteria better, from simply differentiating viral from bacterial infection to identifying ‘hyper bacteria’ – in itself a huge challenge, according to Walsh. “It’s very difficult, for example, for a GP to do this when prescribing,” he says.
“We need GPs to have the option to take a swab or a blood test and get a quick decision on how to target the best treatment.”
The third prong involves close work with a broad spectrum of experts to observe how bacteria behaves in the real world – from outdoors to the built environment, but also in the gut – a highly specialised environment.
The fourth and final prong is to comprehend the impact of human behaviours.
“We need to understand, for example, why patients go to general practitioners wanting antibiotics, and why GPs do not feel empowered to say ‘no’,” Walsh says.
In a global context, this means understanding antibacterial resistance in the context of society.
“There’s no point in imposing a Western solution in Africa – so we need to work closely with international partners, to understand behaviours, social pressures and drivers in different countries,” he says.
Given the project’s multidisciplinary approach, the UK Research Councils are keen to attract individuals who may not recognise that they have something to contribute, and to enable people to talk to each other on a broader scale.
“For example, someone might be an expert mathematical modeller and can apply their knowledge to the field,” Walsh says.
Pharma getting involved
Pharma’s role in combating antibiotic resistance is also clearly nothing if not important. According to Walsh, the UK’s pharmaceutical industry has indeed been significantly engaged in the process.
Key participants range from small biotechs to major players such as GlaxoSmithKline, all of which, he says, “have been given a bit of a hard time”.
The current challenge for pharma is making an antibiotic drug that is able to kill one type of bacteria without harming others – which is of course difficult. In addition, Walsh says, it can take a long time for pharma companies to change direction.
Thus, when the 1980s and 1990s saw a drive for antivirals to combat HIV, hepatitis or influenza, leading in turn to significant infectious disease research at a time when antibiotics worked very well, no one had the foresight to challenge the status quo.
“Turning back to antibiotics is a big shift,” he says. “We are asking drug companies to spend billions of pounds on a drug to be used for a week – when they need a return or they’ll go bust.”
Despite such obstacles, the pharma industry is now engaging in economic and business modelling, as well as input at a scientific level.
At the time of writing GSK, for example, has several antibacterials in very early development. It also has an asset in Phase II; known as 2140944, this is being developed as part of a collaboration entered into by GSK in 2013 with the US Biomedical Advanced Research and Development Authority, aiming to support the development of several antibiotics to fight antibiotic resistance and bioterrorism.
“At GSK we have a long heritage and expertise in antibiotics going back 40 years and we’re committed to continuing our research in this area – we are one of only a handful of companies that still has an active pipeline,” says David Daley, GSK’s director of Media, Global R&D, Pipeline and Product News.
“Tackling antibiotic resistance is a challenge we want to be part of solving, but no one company can do this alone,” Daley says.
“Antibiotics research is one of the areas where we believe taking an open-minded approach to sharing information and engaging in public-private partnerships will help to address some of the key barriers to the development of effective new medicines.”
Daley also notes that, given the incredible complexity of antibiotics R&D, new approaches are needed on a global scale if more companies are to be encouraged to invest in this area.
“This needs to include new economic models and more open minded approaches to sharing information and working with partners across the public and private sectors,” he says.
Where next?
The MRC is indeed asking people to align with both pharma and biotechs at this stage, through a range of partnerships such as sharing drugs or providing man hours but, most importantly, engagement at the earliest stages of research to share ideas.
It aims to encourage initiatives and academic partnership, enthusing and engaging pharma with alternative therapies or vaccination approaches, for example.
“The link with the academic sector may offer new opportunities and new potential, and helps pharma focus on what is really positive,” Walsh continues.
Over the past five to 10 years, he says, pharma has already become significantly more engaged in the academic research environment, merging its happy blend of scientific rigour, project management expertise and technology with the blue-sky-thinking and understanding of basic research areas introduced by academia.
“We are encouraged by their engagement, exemplified by that of GSK,” he says. “Maybe we can do more in the UK to encourage other companies to come back into antibiotics, by helping people with the anti-infectives pipeline, or by partnering with academic groups and other sectors such as IT, engineering, or social media – all of which can contribute.”
Challenges lie ahead
Pharma faces a number of challenges and requirements, not least of which is the double jeopardy presented by scientifically arduous practicalities – such as trying to kill one cell whilst maintaining others.
“Working with scientists, plus the broader discipline of interested parties, will help us overcome some of these scientific challenges,” Walsh says.
“The chief challenge is always going to be the science – how we address scientific elements to get a multi-pronged approach.”
With this in mind, Walsh is sympathetic to arguments by pharma firms stating they require better incentives, such as tax breaks or research and development credits in order to create the new medicines required to tackle antibiotic resistance.
“It is very expensive to make a drug,” he says. The big question then, he adds, is not only how to make great antibiotics, but also how to make them globally.
Models of how to do this do exist, for example via public-partnerships such as the distribution of HIV drugs to sub-Saharan Africa through the US president’s Emergency Plan for AIDS Relief (US PEPFAR) initiative.
Ultimately, he says: “We have to be imaginative. Making a drug is hugely expensive; to de-risk this, we can identify stronger candidates and move forward; improve the business environment; and preserve the drugs we’ve already got through better usage, better diagnoses and better targeting.”
Susie Lunt
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