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Q4 / 2020
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Antimicrobial Resistance AMR
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‘Antibiotics are increasingly victims of their own success.’ Thomas Cueni Director General, International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) and Chair, AMR Industry Alliance
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‘Governments must also provide sustained investments into new ways of tackling drug-resistant infections, including treatments, diagnostic tests and vaccines.’ Dr Manica Balasegaram Executive Director, Global Antibiotic Research and Development Partnership
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Innovative programmatic efforts to stem antibiotic resistance
IN THIS ISSUE
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Framing the issue of antibiotics and bacterial infections within the broader antimicrobial resistance agenda will facilitate programmatic synergy, efficiency and catalyse country level action.
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‘Governments must also provide sustained investments into new ways of tackling drug-resistant infections’ Dr Manica Balasegaram Executive Director, Global Antibiotic Research and Development Partnership
12 ‘AMR will only be solved by looking outwardly, working globally and sharing expertise’ Professor Dame Sally Davies UK Special Envoy on Antimicrobial Resistance
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‘We need to reduce the inappropriate use of both antibiotics and antimicrobials’ Doris-Ann Williams MBE Chief Executive, British In Vitro Diagnostics Association Project Manager: Natalia Sanz Dawson natalia.sanz. dawson@mediaplanet.com Business Development Manager: Roz Boldy Managing Director: Alex Williams Head of Business Development: Ellie McGregor Head of Production: Kirsty Elliott Designer: Thomas Kent Digital Manager: Harvey O’Donnell Paid Media Manager: Ella Wiseman Production Assistant: Henry Phillips Mediaplanet contact information: P:+44 (0) 203 642 0737 E: uk.info@mediaplanet.com All images supplied by Gettyimages, unless otherwise specified
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WRITTEN BY
Dr Haileyesus Getahun Director of Global Coordination and Partnership on AMR, World Health Organization
his week is the World Antimicrobial Awareness Week, which we are marking at the height of the COVID-19 pandemic. This year, the focus of the campaign has widened, from antibiotics to antimicrobials, embracing also antivirals, antifungals and antiparasitic medication. Antimicrobials are used to prevent and treat infections in humans, animals and plants. Antimicrobial resistance occurs when bacteria, fungi, parasites and viruses change over time and cease to respond to these medicines. It is driven by misuse and overuse in humans, animals and plants. Reframing antibiotic resistance Drug resistant infections are harder to treat and increase the risk of transmission and severity of illness, and death. The search for new antibiotics to treat drug resistant bacterial infections continues to be a priority. We need to frame the response to antibiotics resistance within the broader health sector and antimicrobial resistance agenda. This will facilitate programmatic synergy, efficiency and catalyse country level action. Drug resistance is a global challenge Countries of all income levels are reporting alarming levels of antimicrobial resistance. High rates of drug resistant bloodstream bacterial infections have been reported in low and middle income countries. Close to half a million people, mostly in low and middle income countries, developed drug resistant TB in 2019, of which only 38% received treatment. Resistance to antimalarials and insecticides as well as increasing
Close to half a million people, mostly in low and middle income countries, developed drug resistant TB in 2019, of which only 38% received treatment. resistance to HIV drugs threatens the progress made so far. Likewise, Candida auris, a multidrug resistant fungal infection which was first reported in 2009, has now spread to all continents with high mortality rates of up to 60%. Uniting stakeholders for public health response Expanding the campaign from antibiotics to antimicrobials will help to address this complex issue, by engaging key stakeholders and policy makers in a comprehensive public health response, and facilitates leveraging of resources, efficiencies and synergies. For example, the Global Fund to Fight AIDS, TB and Malaria invests US$1 billion a year to build resilient and sustainable health systems with benefits beyond TB, HIV and malaria. Its efforts to improve procurement and supply chains, laboratory and diagnostic capacities and strengthened data systems and use, could have significant impact and revolutionise antibiotic resistance efforts at the country level, with little additional investment. Robust and representative data on drug resistant bacterial infections is urgently needed. It can be generated by modifying and funding existing and common laboratory diagnostic platforms, helping to inform coordinated national and global efforts to stem antimicrobial resistance.
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Europe’s medicine cabinet is running out of new antibiotics But the UK and Sweden may have answers. They are tackling the antimicrobial crisis head on by taking a new approach that turns the current payment system for innovative drugs on its head.
A INTERVIEW WITH
Professor Dame Sally Davies UK Special Envoy on Antimicrobial Resistance
INTERVIEW WITH
Aleks Engel Partner, Novo Holdings and Director, REPAIR Impact Fund at Novo Holdings
WRITTEN BY
Kate Sharma
ntibiotics have been the best deal in healthcare for decades. However, the relatively low cost of drugs, coupled with growing resistance, and declining investment in research and development means that Europe’s medicine cabinet is now looking decisively bare. “We have got a broken system for the R&D and marketing of new antibiotics,” confirms Professor Dame Sally Davies, UK Special Envoy on Antimicrobial Resistance. “We’re seeing rising resistance, but with more medical advances which rely on anti-infectives, we’re running out of options.” In response, the UK and Sweden are pioneering innovative new subscription approaches to address the current market failures by using pull incentives to ensure we have a pipeline of drugs that are fit for purpose and accessible to those who most need them. A trial of the subscription model was launched in the UK over the summer and, from April 2022, the NHS will pay two pharmaceutical companies a set amount for access to their antibiotic product. If successful, it’s hoped that other countries would rollout similar, innovative systems- and create meaningful incentives for global investment in R&D.
The severity of the situation can’t be underestimated.
Paid for by REPAIR Impact Fund
Addressing market failures To put things in context, no new class of antibiotics has been discovered and made available for routine treatment since the 1980s and of the 25 new chemical entities that were registered between 1999 and 2014, only 12 had registered sales in more than 10 countries. These statistics paint a worrying picture and highlight the need for action. Europe is now at risk of missing out on new treatments because antibiotic developers who cannot justify the expense of developing, registering and launching their drugs here. Aleks Engel, Director of the REPAIR Impact Fund at Novo Holdings, who invest in the discovery and early-stage development of therapies targeting
resistant microorganisms, believes the severity of the situation can’t be underestimated. “Even the drugs that despite the difficult economics manage to prove themselves in clinical development are not being registered and sold in Europe, because they are owned by undercapitalised small and medium sized companies that cannot afford to launch new products or even put in a new drug application here,” he says. “The Netflix model,” as Engel refers to it, seeks to address the system failures by providing a guaranteed level of revenue so drug developers know precisely what they are going to get, regardless of how much of the drug they sell. Ensuring good stewardship While this approach provides security for the drug developers, there are significant expectations too. The two antibiotics currently being contracted by the UK in the trial will capture benefits to the NHS and wider society; they will also be judged for their commitment to antimicrobial and environmental stewardship; and have robust plans for surveillance. The overuse and misuse of antibiotics have been major contributing factors to antimicrobial resistance, so the model seeks to remove the incentive for companies to sell more than is absolutely necessary.
“Better stewardship equals longer efficacy”, confirms Davies. Underpinning modern medicine The reality is, antibiotics underpin modern medicine. Whether it’s transplant surgery or ongoing care of patients undergoing chemotherapy, success relies on robust effective antibiotics being readily and affordably available worldwide. The UK’s Global AMR Innovation Fund supports innovation around the world to develop new vaccines, treatments and tests that are specifically tailored to low- and middle-income countries. With consistent stewardship, nations would not just save antibiotics or build back from COVID-19 but build up global preparedness for the future. Drug resistance knows no boundaries and failure to act will have repercussions across the globe. Europe can certainly take a lead on innovating new mechanisms and approaches, but cannot create sustainability alone. “We need much more global collaboration. If these approaches are feasible, other counties will try similar innovative mechanisms” confirms Davies. Progressing the battle against antimicrobial resistance requires both courage and investment. The UK and Sweden is taking the lead but need others to follow.
Read more at repair-impact-fund.com
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How to change the fight against AMR?
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multi-directional approach is critical to win the war against antimicrobial resistance (AMR). SMEs are developing interventions that tackle AMR in six different areas to meet patients’ requirements.1
Thirdly, the cure of an established infection is sought through direct inhibition or killing of the causative pathogen. Novel strategies can complement the approach. They aim at increasing the speed to cure and minimising antibiotic exposure time, re-arming the immune system or dismantling the very specific resistance or tolerance mechanisms. Protecting the body from tissue or microbiota damage because of infection is the fourth requirement and is key to avoiding further, potentially long-term medical complications of infectious disease. Limiting the pathogen’s ability to develop or spread resistance is the fifth requirement and is critical in putting the brakes on the AMR juggernaut. Finally, blocking the spreading ability of the pathogen itself helps to break the dynamics of contamination at a community level.
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Novel interventions to stem the rising tide of AMR are urgently needed. SMEs are the innovation engine in this field.
Limiting the pathogen’s ability to develop or spread resistance is the fifth requirement and is critical in putting the brakes on the AMR juggernaut.
Diversifying the field of fight against AMR The first requirement is to avoid infection. This can be done through vaccination, restoration and maintenance of optimal immune function, highly specific weapons that prevent or correct dysbiosis and a ‘breach’ of the microbiota by pathogenic microbes. Accurate and rapid diagnosis of bacterial pathogens is the second requirement, so that the appropriate antimicrobial therapy can be administered at the earliest opportunity. This will avoid empirical treatment and its consequent risks of resistance wherever possible.
WRITTEN BY
Deborah O’Neil Board Member, BEAM Alliance
Market and regulation: the missing link in the evolution of AMR fight However, this promising landscape of SME generated solutions to AMR faces a paradox. Diversity and novelty in antimicrobial approaches is critical in changing the trajectory of AMR. But current evaluation methods (e.g. Minimum Inhibitory Concentration) are unable to demonstrate any benefit outside the killing/inhibiting effect and in turn, the potential monetary and societal value of these next-gen antimicrobial interventions. New evaluation methods are needed. Furthermore, the AMR field has been ‘tarnished’ somewhat by previous market failures of antibiotic companies; failures that are not directly relevant to the business model and case for next-gen SME-created interventions now in the pipeline, but nonetheless for the time-being, still jeopardise the chances of commercial success for SMEs. These problems must be solved. Infectious disease is a rapidly evolving field. Since pathogens are evolving and develop resistance, SMEs have also evolved and changed their way of thinking, creating new approaches to disarm those resistance. The regulatory and financial framework must now catch up to enable the potentially gamechanging products developed by SMEs to reach patients. References
1. This categorization work was run by the VeRI BEAM Network, funded through a JPIAMR-VRI Network Call. For more information about JPIAMR and AMR research, please visit: jpiamr.eu.
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Improving old antibiotics – does it make any sense? It does make complete sense. Most of the antibiotics of the “golden age of antibiotic discovery” have now been replaced by their improved versions.
T WRITTEN BY
Professor Martti Vaara M.D., Ph.D. CEO, CSO, Northern Antibiotics Oy
Paid for by Northern Antibiotics
his has happened to the archetypical betalactam, penicillin G. Now we use its fourth generation. The same is true of the first cephalosporin, cephalothin. Now we use its fifth generation. Similarly, a majority of the well-known antibiotics, such as tetracyclines, aminoglycosides, macrolide antibiotics and quinolones, are today represented by their latest generation of more efficacious and tolerable versions. True, brand new antibacterial compounds, isolated from nature or designed in silico, with an entirely new target or mode of action, are preferred by the investors and funding agencies. Rightly so. However, starting from scratch, the development is risky, and surprises may loom even at a late stage. Working with the old antibiotics, the good and bad characteristics of the compounds are already known. You can plan your modifications
accordingly and predict the outcome with a certain degree of accuracy. Today, we still use the first generation of polymyxins Polymyxins were discovered in 1947. Their clinical use, however, was practically abandoned in the 1960s due to nephrotoxicity (rapid deterioration of kidney function) and because bettertolerated drugs belonging to other antibiotic classes were discovered. Now, however, polymyxins have resurged as the last-resort drugs against extremely multi-resistant strains, despite the fact that their nephrotoxicity forces clinicians to administer doses that are lower than those required for optimal efficacy. Time for the next generation of polymyxins? Polymyxins bind strongly to the brush-border membrane (BBM) of the proximal tubular kidney cells and this results in their nephrotoxicity. Northern Antibiotics have designed,
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Complicated urinary tract infection (cUTI) which often leads to life-threatening blood-stream infection is the biggest single indication of the use of hospital antibiotics. at preclinical stage, polymyxin derivatives1 that bind to the BBM at the rate of one tenth of that of the old polymyxin and that are some three times less nephrotoxic. On top of that the polymyxin derivatives are some 10 times more efficient in treating experimental E. coli urinary tract infection. Improved efficacy means lowered doses required and, you guess, the lowered doses mean that the adverse effects may be even further reduced. The improved polymyxins may be most useful in treating complicated urinary tract infection (cUTI) which often leads to life-threatening blood-stream infection and is the biggest single indication of the use of hospital antibiotics. References 1. Vaara M. 2019. Polymyxins and their potential next generation as therapeutic antibiotics. Frontiers in Microbiol 10, article 1689. doi: 10.3389/fmicb.2019.011689. Read more at northernantibiotics.com
Filling the innovation void to tackle AMR A renewed and sustainable pipeline of effective antibiotics is vital to modern medicine. New thinking offers a patient-centric approach to antibiotic development to tackle resistance and improve health outcomes.
INTERVIEW WITH
Clive Mason Vice President, Anti-Infectives Research, Summit Therapeutics WRITTEN BY
Kate Sharma
Paid for by Summit Therapeutics
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ecent antibiotic drug approvals have largely been based on existing antibiotic classes, providing a stop gap, but not a long-term solution. “The most recent market launches have been incremental improvements on those old classes of drugs, but the expectation is that resistance to those will continue to develop,” confirms Clive Mason, Vice President of Anti-Infectives Research at Summit Therapeutics, a US/UK based antibiotic discovery company. An alternative is a more personalised approach that harnesses precision agents that act through new mechanisms, targeting specific pathogens to overcome existing resistance mechanisms. Protecting the whole person However, drug resistance is not the only issue that needs to be considered. The detrimental impact that the use of broad-spectrum antibiotics can have on a patient is less well understood, but no less important. Since broadspectrum agents have the power to kill a range of bacteria – both good and bad – overuse of these drugs can perturb the gut microbiome and weaken an
individual’s immune system. “There is growing evidence that maintaining a diverse microbiome is a key health protection mechanism in humans,” continues Mason. “Broad spectrum agents can obliterate the microbiome and leave patients in a compromised state.” For example, dysbiosis, a disturbance of the gut microbiome, is a common side effect of extensive antibiotic use and can lead to infection by opportunistic pathogens such as Clostridioides difficile. More targeted therapies that are sympathetic to the microbiome could address the infecting bacteria whilst protecting against further disease. Targeting through diagnostics Of course, a more targeted approach is reliant on precisely identifying the type of bacterial infection through rapid diagnosis. “Some systems are in use in hospitals, but the key is being able to diagnose rapidly and accurately to allow the physician to prescribe the right drug.” explains Mason. The good news is that progress on targeted agents is being made. Summit Therapeutics is currently advancing a number of programmes including
We are dependent on antimicrobials for so much of modern medicine. To safeguard this, and save lives, we need to embrace and fully exploit antibiotic innovation. Phase 3 clinical trials of a novel antibiotic designed to not only target C. difficile infection but also reduce the debilitating burden of disease recurrence. Success for new antibiotics is not simply dependent on the clinical outcomes, though. Commercial viability is an on-going tension in antibiotic development that needs reconciling for longer term sustainability. “Even with the current antibiotic market challenges, we at Summit believe that success is possible by clearly differentiating over existing therapies to ensure clinical use and reimbursement” concludes Mason. We are dependent on antimicrobials for so much of modern medicine. To safeguard this, and save lives, we need to embrace and fully exploit antibiotic innovation.
For more information on Summit Therapeutics, its strategy and programmes visit: summittxinc.com
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Saving lives with vaccines and antibiotics
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hile we count the months until a safe and effective COVID-19 vaccine is available, it is easy to forget that there are many existing vaccines that play a crucial role in fending off other potential health crises. One such crisis is antimicrobial resistance.
Certain vaccines help prevent diseases that might require the use of antibiotics, as a result reduce their use and misuse which safeguards their effectiveness. For example, the pneumococcus bacteria that leads to pneumonia, earache, sinusitis and many more serious infections can be avoided thanks to pneumococcal vaccine. Worldwide, there are around 14.5 million global pneumococcal cases in one year alone. With more widespread Streptococcus pneumoniae vaccination, we could avoid 11.4 million days of antibiotic use per year in children under five.2
The role of antibiotics Antibiotics are used widely in medicine today. They are used to treat pneumonia, plus urinary tract and blood stream infections. They also stave off infections when receiving chemotherapy and after having a Encouraging wisdom tooth out. responsible use Today, it is estimated that While COVID-19 of antibiotics AMR takes 700,000 lives is a virus, and As the global antibiotics serve no community focuses each year; and if we do not purpose in treating it its efforts on take more care, this number all directly, antibiotics tackling COVID-19, will only get worse.1 are essential when it must factor into its treating COVID-19 efforts the prudent bacterial complications. use of antibiotics. However, antibiotics are increasingly It must not lose sight of the victims of their own success. Their wide importance of uptake of those use has accelerated the natural process vaccines that protect people from of bacteria adapting, so more bacteria illness that would or could require are becoming resistant to antibiotics. antibiotic treatment. These so-called superbugs are Failure to do so, will only lead to the result of a problem known as the increase of AMR; and undermine antimicrobial resistance (AMR). further our health systems and modern Today, it is estimated that AMR takes medicine as we know it. 700,000 lives each year; and if we do not take more care, this number will References 1. https://www.who.int/antimicrobial-resistance/interagencyonly get worse.1 Using vaccines to prevent diseases There is some good news, and this is where existing vaccines come into play.
coordination-group/IACG_final_report_EN.pdf?ua=1 2. https://www.who.int/immunization/monitoring_surveillance/ burden/estimates/Pneumo_hib_2000/en/index2.html
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The coronavirus pandemic has brought vaccines into sharp focus; but we must not forget their importance in tackling the rise of superbugs.
Thomas Cueni Director General, International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) and Chair of the AMR Industry Alliance
Pharma invests $1 billion into antibiotic pipeline The world is losing its most powerful tool in healthcare: antibiotics. The reason is rapidly rising antimicrobial resistance (AMR). Industry is taking steps to help tackle the crisis.
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MR not only threaten lives, it undermines every aspect of modern medicine. COVID-19 has shown us the tremendous public health and economic consequences when we don’t have the vaccines and treatments we need. AMR could have even greater consequences – unless we take action now. The pipeline problem We urgently need new antibiotics, but there are few in the pipeline because of a paradox: despite the huge societal costs of AMR, there is no viable market for new antibiotics. New antibiotics are used sparingly to preserve effectiveness, so in recent years multiple antibiotic-focused biotechs have declared bankruptcy due to the lack of commercial sustainability. The remaining biotechs are not able to find investors to support their antibiotic R&D, particularly the later stages of clinical research. This funding “valley of death” means that many antibiotics in the pipeline are in danger of never reaching patients. Pharma taking action To bridge this gap, the AMR Action Fund aims to bring two to four new antibiotics to patients by the end of the decade. The companies involved have raised so far nearly US$1 billion of new funding to support antibiotic clinical research that addresses the most-resistant bacteria. The aim is to overcome key technical and funding barriers of late-stage antibiotic development through the injection of both pharma expertise and capital into biotechs. The Fund will also work with governments to ensure there is a sustainable pipeline of new antibiotics to fight superbugs.
Silas Holland Head of External Affairs, AMR Action Fund
While COVID-19 caught the world unprepared, AMR is a predictable and preventable crisis that we can’t afford to ignore. Decisive government action needed Putting in place the necessary policy reforms to support antibiotic innovation will take time – time the world doesn’t have as the fragile antibiotic pipeline is near collapse. The pharmaceutical industry has stepped up to ensure no promising science is delayed or stopped. However the AMR Action Fund is just a temporary and time limited bridge that will only work if key governments make the necessary reforms to create a sustainable market. There have been some promising proposals to change the way antibiotics are valued and reimbursed, but more action is needed from governments. While COVID-19 caught the world unprepared, AMR is a predictable and preventable crisis that we can’t afford to ignore. Together, we must act now to safeguard our future from this global threat. Over 20 pharmaceutical companies have invested nearly US$1 billion into the AMR Action Fund. The concept was developed by the International Federation of Pharmaceutical Manufacturers and Associations in collaboration with the World Health Organization, European Investment Bank, and Wellcome Trust. AMRActionFund.com
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There’s new life in tried-and-tested drugs A vital class of antibiotics is on the verge of being saved thanks to European investment and collaboration.
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Dr Sven Hobbie Founding CEO, Juvabis
Written by: Kate Sharma
Paid for by Juvabis
n estimated 500 million daily doses of a class of antibiotics known as aminoglycosides are prescribed globally every year to fight bacterial infections. Their effectiveness is being undermined by antimicrobial resistance. Swiss-based Juvabis are currently progressing a new type of aminoglycoside in phase 1 clinical trials. The World Health Organization considers that aminoglycosides should be stocked by every major hospital in the world, calling them “Essential Medicines”. Medical doctors rely on aminoglycosides being extremely efficient and life-saving drugs. But, as Dr Sven Hobbie, Founding CEO of Juvabis points out, “For life-threatening infections common also in Europe, like Acinetobacter bacteria, current aminoglycosides simply don’t work in one of every two patients. In some countries with widespread resistance they do not work at all.” Hobbie hopes that recent breakthroughs in Juvabis will “ensure that doctors will continue to make use of this truly amazing class of drugs whenever they need them to save human lives.”
A long overdue breakthrough Aminoglycosides were first discovered in the 1940s and have helped to rapidly reduce mortality rates around the world ever since. As Hobbie explains, “Since 1957, all new aminoglycosides brought to market for improving the treatment of patients have been minor modifications of what was already available before. We’re the first company introducing the next great breakthrough.” For some, just relying on “known” antibiotic classes might not go far enough and there remains a need for completely new types of drug. “Hopefully the industry will also find totally new types of antibiotic in the next 20 years. In the meantime, our “best-in-class” drug combines the best of both worlds: a much needed, overdue innovation that works also against superbugs and, at the same time, a safe-bet in a tried-and-tested, class of drugs that doctors will rely on”, points out Hobbie. European collaboration IMI-ENABLE is a European Commission funded group that brings together pharmaceutical companies, academics and biotech companies to collaborate
in the development of new drugs. Proposals have to meet strict criteria, fulfil key clinical milestones and undergo extensive scrutiny on the way.
Hopefully the industry will also find totally new types of antibiotic in the next 20 years. Thanks to this collaboration Juvabis have made very fast progress, bringing their new drug to clinical phase 1 in less than four years. “From many points of view, we are de-risked and a safe investment,” explains Hobbie. The funding from IMI-ENABLE will support the development of the drug through phase 1 trials. Now the company is offering an opportunity for investment and collaboration to progress into clinical phase 2. While there is still some way to go before the drug can make it into every major hospital around the world – the team are quietly optimistic that there is a promising new life for aminoglycosides.
Read more at juvabis.com
New antibiotics alone are not the answer to AMR AMR is a growing threat to global health. But, as well as developing new drugs, which bacteria may also grow resistant to, should we not be making better use of those we already have?
INTERVIEW WITH
Dominic De Souza Global Head, AntiInfectives Sustainability and AMR Program, Sandoz, the Novartis generics division
Written by: Amanda Barrell
Paid for by Sandoz
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ntimicrobial resistance (AMR) is one of the biggest threats facing the world today, but innovation alone – while a critical part of the solution – will not save the millions of lives at stake. We need a balanced approach, says Dominic De Souza, Global Head of the Sandoz Anti-Infectives Sustainability and AMR Program, and board member of the AMR Industry Alliance. “There is no “silver bullet” that will magically end AMR. This is a natural phenomenon, driven by evolution, so every new drug will also be subject to resistance.” De Souza says the global healthcare community needs to focus its efforts equally across four related areas: manufacturing, access, responsible use, and innovation. Sustainable manufacturing The “starting point” is to ensure environmentally friendly manufacturing standards worldwide, says De Souza. “Antibiotics released to the environment, mostly through effluents, can be a significant cause of AMR spread.” Ensuring reliable and environmentally friendly supply is the first step to
driving sustainable access to appropriate antibiotics worldwide. Because the key is not simply to reduce the use of antibiotics, it is to ensure access to the right medicine, for the right patient, at the right time.
Responsible use means providing the right care in the right place at the right time.
Securing access “Use of antibiotics in low- and middleincome countries is increasing steadily, and that’s a good thing. But there is still a way to go, because millions of people – mainly children – still die from lack of access to antibiotics,” says De Souza. Access is not a problem confined to LMICs. COVID-19 has demonstrated how dependent the world is on reliable supply of essential medicines, particularly antibiotics. Access is also an economic issue. Most antibiotics have been off patent for many years, meaning prices have reached often unsustainably low levels, and this increasingly drives outsourcing, market exits and, ultimately, drug shortages. De Souza notes that Sandoz, the leading global supplier of generic antibiotics, is the only company that
still has a vertically integrated antibiotics supply chain based in Europe. Responsible use Stewardship means providing the right care in the right place at the right time, in a responsible way. That means, for instance, stopping over the counter sales of unprescribed antibiotics. It is critical because the vast majority of antibiotics do still work, either alone or in combination. The priority now is to keep it that way, by working together to prevent overuse, underuse, or misuse. De Souza concludes: “Antibiotics are not a commodity, but life-saving drugs that also enable everyday healthcare interventions including open surgery and chemotherapy. Let’s work together to keep it that way.”
Read more at sandoz.com
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The world better be prepared for a silent pandemic! Antibiotics have shaped the way we prevent and treat bacterial infections, however without quick interventions required in the field, we could be on the cusp of losing the battle to antimicrobial resistance (AMR), the silent pandemic.
The parallels between AMR and COVID-19 COVID-19 has clearly shown how unprepared we are as a humanity and offers the perfect preamble to an AMR driven pandemic scenario. There have been 1.2 million deaths globally, with an estimated loss of global GDP around 8 trillion USD. It is estimated that 15% of the COVID-19 deaths are due to secondary infection caused by resistant bacteria. Viruses and bacteria hunt in pairs! The numerous trails of helpless immigrant labour walking back home across the Indian subcontinent, when India announced its total lockdown to deal with COVID-19, presented a lasting image, the “shadow trailer” of the impending disaster owing to AMR. To offset the repeat of this scenario, what is required is a coordinated global initiative to both protect existing solutions and to invest in urgently needed diagnostics and antibacterial therapies. World leaders, particularly those in LMICs, need to treat AMR as a ‘critical medical infrastructure’, and commit resources to promote and sustain innovation in this space. Not doing so will result in death and economic destruction far worse than what we’re currently witnessing! WRITTEN BY
Anand Anandkumar PhD Co-founder and CEO, Bugworks Research Inc (USA, India)
The drug resistance pandemic is already here
©Church of the King/ Unsplash
I
t all started in 1928 with Alexander Fleming and the discovery of penicillin. Antibiotics changed humanity more than any other innovation of the 20th century. Over the coming decades, what followed was the ‘golden age’ of antibiotic innovation and society prematurely claimed that we had won the infection battle. Today we know that the world faces a huge challenge in not having enough solutions against antimicrobial resistance (AMR). According to the UK government sponsored O’Neill report of 2016, AMR takes more than 700,000 lives every year and that if left unchecked could take up to 10 million lives in a couple of decades. This would have major devastating effects on low to medium income countries (LMICs). The UN and WHO reports also paint a dire picture: by 2030, antimicrobial resistance could force up to 24 million people, in LMICs, into extreme poverty.
COVID-19 has demonstrated addressing a pandemic requires a global coordinated effort, and no country can do it alone.
D WRITTEN BY
Dr Manica Balasegaram Executive Director, Global Antibiotic Research and Development Partnership
rug-resistant infections kill at least 700,000 people every year, a number projected to increase exponentially unless resistance is tackled. The consequences of not addressing this ‘silent’ pandemic of drug resistance could result in an unpredictable future, in which we are unable to safely perform operations and chemotherapy, or treat common infections like pneumonia, urinary tract infections and infections in newborns. There is an opportunity to avert this catastrophe through strong leadership, collaboration and investment in measures to fight drug resistance. But we must act now. The cost of failing to adequately prepare for COVID-19 is already measured in over one million lives lost and trillions of dollars in economic damage. A similar situation could occur for the pandemic of drugresistant infections. Learning lessons from COVID-19 As outlined in a recent report by the Global Antibiotic Research and Development Partnership (GARDP), the coronavirus outbreak has demonstrated that preparing for pandemics requires a globally joined-up effort, and no country can do it alone. It has also shown that our ability to control infections must ensure affordable access to prevention, testing and treatment, for everyone. The One Health concept is particularly critical to tackling the pandemic of drug-resistant infections, which connects people’s health to the wellbeing of animals and our environment. A One Health approach is essential in designing and rolling out programmes, policies and research that bring together disparate sectors.
Governments must also provide sustained investments into new ways of tackling drug-resistant infections, including treatments, diagnostic tests and vaccines. Drug-resistant infections move silently within populations and between animals, humans and environments; they know no boundaries, and neither should our responses. Increasing investment to find new solutions Unlike novel viruses, we already know the drug-resistant microbes we are up against and what it will take to combat them. A critical first step requires that information about resistance prevalence is routinely fed into global surveillance systems. Greater alignment of groups working on infection prevention and control, as well as factors influencing resistance in humans, animals and the environment, is equally essential. Governments must also provide sustained investments into new ways of tackling drug-resistant infections, including treatments, diagnostic tests and vaccines. COVID-19 has driven home that our health and well-being are inextricably linked, regardless of where we live. We must seize this opportunity to radically step up our response to drug-resistant infections. We need to prepare ourselves to handle the insidious nature of this pandemic, where the true extent of the damage too often remains invisible. Read more at globalcause.co.uk
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Reasons to be optimistic about new antibiotic development Two years ago, the outlook for viable antibiotics looked bleak. Now policymakers have realised the scope of the problem, while a number of new innovations are in the pipeline.
Dr Christopher Burns President and CEO, Venatorx Pharmaceuticals
Dr Joseph Larsen Vice President, Strategic Portfolio Development, Venatorx Pharmaceuticals
Written by: Tony Greenway
Paid for by Venatorx Pharmaceuticals
B
acteria are clever, says Dr Christopher Burns, President and CEO of Pennsylvaniabased pharma company, Venatorx Pharmaceuticals. You can put them under pressure with an antibiotic, but eventually they’ll find a way to wear it down and decrease its effectiveness. They always do, and always will. “There’s an inevitability to antimicrobial resistance (AMR),” notes Dr Burns. “It’s unavoidable, which is why every 15 - 20 years the world needs a new wave of antibiotics.” Without them, infections will become harder, or even impossible, to treat. Worryingly, in recent times, pharma companies and policymakers have taken a head-in-the-sand mentality to antibiotic-resistant infections. When one antibiotic has lost its effectiveness — or even stopped working altogether — the medical establishment has simply ditched it and moved on to the next. But the repercussions are potentially dire. Creating new antibiotics that are safe and effective To address the next wave of AMR, Dr Burns believes that new broadspectrum antimicrobials — which have the potential to affect both grampositive and gram-negative bacteria — are needed. “It makes more sense to develop broad-spectrum agents,” he says. “Physicians don’t have the luxury of waiting for lab results (which narrowspectrum agents would require) and want to treat infections as broadly and as quickly as they can with something that’s safe and dependable.” That, however, is harder than it sounds because many pharma companies have been reluctant to get involved in antibiotic development. Not surprisingly, they dislike being exposed to significant costs and risk for an uncertain return. Therefore, an improved economic model is needed — one that incentivises and supports antibiotic innovation and ensures that medicines are available when needed and new drugs are constantly in the pipeline. The pandemic is increasing the need for antibiotics Thankfully, in the United States, two pieces of legislation — the Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms (DISARM)
©IMAGE PROVIDED BY VENATORX PHARMACEUTICALS
INTERVIEW WITH
Act of 2019 and the Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act — may provide the incentives pharma companies need. “It’s early days, but at the very least there is now explicit acknowledgement that the marketplace for these drugs is broken,” says Dr Joseph Larsen, Vice President, Strategic Portfolio Development at Venatorx Pharmaceuticals. “I think the discussion among policymakers has shifted from ‘is there a problem?’ to ‘there is a problem — so what kinds of initiatives should we roll out to solve it?’ DISARM and PASTEUR may provide a step towards transformational change in the market that will allow companies like ours to thrive, grow and continue making new and novel antimicrobial agents.” COVID-19 has increased demand for new antibiotics, because a significant percentage of people with the virus progress to a secondary bacterial infection. “COVID-19 is another reason why we’re going to need new drugs,” stresses Dr Burns. “But these drugs don’t drop from the heavens. Someone has to produce them.” Two years ago, pessimism about the future of new antibiotic production was palpable, admits Dr Burns. Now
Therefore, an improved economic model is needed — one that incentivises and supports antibiotic innovation and ensures that medicines are available when needed and new drugs are constantly in the pipeline. a number of interesting developments give cause for optimism. For example, Venatorx Pharmaceuticals has an innovative intravenous asset (one which uniquely addresses both serine- and metallo-beta-lactamases resistance) in phase 3 trials, which has prompted partnerships with The Global Antibiotic Research and Development Partnership (GARDP), Everest Medicines, and Biomedical Advanced Research and Development Authority (BARDA). In addition, the company also has a best-in-class oral agent in phase 1 trials. “It’s not just us,” says Dr Burns. “Our friends and competitors are doing some interesting work, while big pharma is seeing the value of being productive players in this space. Plus, there are some serious policy initiatives underway. So, I’m optimistic that things are changing.”
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Updates to the Core Elements of Hospital Antibiotic Stewardship Programs
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CDC updated the hospital Core Elements to reflect both lessons learned from five years of experience as well as new evidence from the field of antibiotic stewardship. ©IMAGES PROVIDED BY BIOMÉRIEUX
Optimising the use of antibiotics is critical to effectively treat infections, protect patients from harm caused by unnecessary antibiotic use, and combat antibiotic resistance.
A WRITTEN BY
Dr. Lauri Hicks Director, Office of Antibiotic Stewardship in the Division of Healthcare Quality Promotion, CDC
ntibiotic stewardship programs can help clinicians improve clinical outcomes and minimise harm by improving the prescription of antibiotics. In 2019, Centers for Disease Control and Prevention (CDC) updated the hospital Core Elements to reflect both lessons learned from five years of experience as well as new evidence from the field of antibiotic stewardship. Major updates to the hospital Core Elements include: Hospital Leadership Commitment: Dedicate necessary human, financial and information technology resources: • The 2019 update has additional examples of hospital leadership, and the examples are stratified by “priority” and “other”. • Priority examples of hospital leadership commitment include: emphasis on the importance of leadership having dedicated time and resources to operate the antibiotic stewardship program effectively. It is also ensuring that the program’s leadership has regularly scheduled opportunities to report stewardship activities, resources and outcomes to senior executives and hospital board. Accountability: Appoint a leader or co-leaders, such as a physician and pharmacist, responsible for program management and outcomes. • The 2019 update highlights the effectiveness of co-leadership between the physician and pharmacy, which was reported by 59% of the hospitals responding to the 2019 NHSN Annual Hospital Survey. Pharmacy Expertise (previously “Drug Expertise”): Appoint a pharmacist, ideally as the co-leader of the stewardship program, to lead implementation efforts to improve antibiotic use. • This Core Element was renamed “Pharmacy Expertise” to reflect the importance of pharmacy engagement for leading implementation efforts to improve antibiotic use. Action: Implement interventions, such as prospective audit and feedback or preauthorisation, to improve antibiotic use.
• A new category of nursing-based actions was added to reflect the important role that nurses can play in hospital antibiotic stewardship efforts. Tracking: Monitor antibiotic prescriptions, impact of interventions, and other important outcomes like C. difficile infection and resistance patterns. • It is important for hospitals to electronically submit antibiotic use data to the National Healthcare Safety Network (NHSN) Antimicrobial Use (AU) option for monitoring and benchmarking inpatient antibiotic use. • Antibiotic stewardship process measures were expanded and stratified into “priority” and “other”. • Priority process measures emphasise assessing the impact of the key interventions, including prospective audit and feedback, preauthorisation, and facilityspecific treatment recommendations.
Reporting: Regularly report information on antibiotic use and resistance to prescribers, pharmacists, nurses, and hospital leadership. • The 2019 update points out the effectiveness of provider level data reporting, while acknowledging that this has not been well studied for hospital antibiotic use. Education: Educate prescribers, pharmacists, and nurses about adverse reactions from antibiotics, antibiotic resistance and optimal prescribing. • The 2019 update highlights that case-based education through prospective audit and feedback and preauthorisation are effective methods to provide education on antibiotic use. This can be especially powerful when the case-based education is provided in person (e.g., handshake stewardship). • The 2019 update also suggests engaging nurses in patient education efforts.
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How better diagnostics can support clinicians in infection control Diagnostic testing has taken centre stage as the world attempts to control COVID-19, and this technology has the power to beat antimicrobial resistance as well.
INTERVIEW WITH
Chris Cook, PharmD, PhD Head, US Medical Affairs, bioMérieux
INTERVIEW WITH
John Hurst, PharmD, BCIDP Sr. Director, Antimicrobial Stewardship, bioMérieux
WRITTEN BY
P
ublic awareness of the need to accurately test for an infection has been heightened by COVID-19, and even more so as the northern hemisphere heads into respiratory virus season. For Dr. John Hurst, Sr. Director of Antimicrobial Stewardship at bioMérieux, the pandemic has helped give a voice to the argument for cost-effective diagnostic investments. He says: “I think COVID-19 has taught us that it all starts with a test. Earlier and more proactive diagnostics have the potential to take one day off length of stay, making a $100 test worth thousands in savings. That’s a policymaker’s easiest decision to make.”
Global public health challenge The World Health Organization (WHO) describes the problem of antimicrobial resistance (AMR) as a major threat to global public health. It estimates that without action, within a decade, global economies will face ruin, due to the increasing ineffectiveness of our medicines. According to the WHO, there are countries where antimicrobial medicines are already useless in more than half of patients. This is resulting in prolonged illness in working populations, financial challenges to health systems and interruptions to food production and supply. With emergent viruses now high on the political agenda - and signs that some viral strains are also now becoming resistant to existing treatments - never has there been a better time for health leaders to act.
The technology exists already. Clinical surveillance just needs more of a political will and an investment, perhaps, to make it more of a reality. Then we can actively work to mitigate outbreaks in real-time, and strategically deploy needed resources based on data.
Ailsa Colquhoun
AMR is a slow burning issue, but it has very complex effects across a wide range of activity: agriculture, hospitals, nursing homes and food production.
©IMAGES PROVIDED BY BIOMÉRIEUX
However, until recently the use of rapid diagnostic technology has been limited, leaving clinicians in the empiric therapy phase to ‘guess’ what the causative pathogen of the infection is, says Dr. Chris Cook, Head of US Medical Affairs at bioMérieux. “The very first thing a clinician tries to do is determine the diagnosis and what is causing it. But until the clinician can rule out other potential causes, they’re forced to play defence and that often means giving a broad-spectrum antibiotic to cover everything it could be.”
Affecting a global response Several factors are important in the delivery of an effective global response to antimicrobial resistance, and for Dr. Hurst, the first of these is investment in diagnostic tests that give faster results. Effective, accurate results within minutes while the patient waits are already available. He says, “To understand why an antibiotic may not be necessary, people need to be able to walk away with objective evidence and a specific course of action.” Secondly, health systems and organisations need to be able to share data and knowledge, for example, which pathogens are in circulation, at what scale and where to provide the evidence to inform effective clinical decisionmaking. Dr. Hurst says, “The technology exists already. Clinical surveillance just needs more of a political will and an investment, perhaps, to make it more of a reality. Then we can actively work to mitigate outbreaks in real-time, and strategically deploy needed resources based on data.” Thirdly, says Dr. Cook, is the need to encourage leadership within the system to ensure everyone is working towards the same, long-term goal. He says, “The hardest thing in any type of stewardship is that you may be taking a harder course in the short-term, looking at the larger picture of consequence for the benefit of the longer-term. “Real leadership involves supporting people towards the realisation that what’s easiest for them, may not be the best for us. Changing human behaviour is never going to be a quick and easy change like the turning of a light switch. It’s going to be a slow and gradual move, one degree by one degree.” Unlike COVID-19, AMR is not an issue that will affect global economies overnight, but that does not mean the world can relax about its threat says Dr. Hurst. “AMR is a slow burning issue, but it has very complex effects across a wide range of activity: agriculture, hospitals, nursing homes and food production. With current projections it will far exceed the impact of COVID-19. For that reason, we must use all of the tools in our toolbox to mitigate the risk of AMR and slow its spread.”
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AMR is a responsibility for us all: Collaborative action is the solution
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harmaceutical companies are working to stem the rise of antimicrobial resistance (AMR), but success requires a cooperative approach. Amalia Adler-Waxman, who leads Environmental, Social and Governance (ESG) at Teva, says: “As one of the world’s largest manufacturers of antibiotics and their active ingredients, Teva is committed to tackling the global challenge of AMR. That includes reducing pharmaceuticals in the environment, ensuring access to qualityassured antibiotics, and working collaboratively with all stakeholders.”
Antibiotics have literally doubled life expectancy. They are a precious resource to be optimally used, not abused, and this is a global problem because bacteria know no borders. Environmental stewardship As a board member of AMR Industry Alliance, the company has a longterm commitment to minimise antimicrobial discharges across 100% of production and 50% of antimicrobial supply chain by 2030. This approach illustrates the necessity for collaboration among all stakeholders, including the pharmaceutical sector. Richard Pickup, who leads Environment, Health, Safety, and Sustainability at Teva, says: “Of all the pharmaceuticals entering the environment, only 2% come from production waste. Unused medicines, often from people discarding boxes of inappropriate medicines, account for 10%. The vast majority – nearly 90% - enter the environment because of patient use, compounded by poor water treatment systems in hospitals and cities. “This means that AMR is everyone’s concern. Patients, healthcare providers, governments and manufacturers need to work together on this issue.”
Amalia Adler-Waxman VP, Global Head, Environment, Social, Governance, Teva Pharmaceuticals
There is a role and responsibility for all of us when it comes to fighting AMR. Local authorities, healthcare systems, national governments, the public and the pharmaceutical industry must all work as a team to tackle AMR.” Access can reduce AMR Shortages of antibiotics also spread AMR, says Giancarlo Francese, who oversees access-to-medicines initiatives on the ESG team at Teva. “In some countries, especially in Africa, shortages of antibiotics mean that doctors are forced to treat bacterial infections with the only antibiotics they have – which may not be specifically aimed at the targeted infection.” This can mean that the target bacteria are not fully eliminated and become resistant to the antibiotics. “This is how shortages of certain antibiotics can drive up levels of AMR,” says Francese. Collaboration drives development In addition, Teva joined alongside more than 20 pharmaceutical companies a new initiative known as the AMR Action Fund. Its aim is to bring two to four new antibiotics to patients by 2030. The fund will invest $1 billion and provide expertise to help antibiotics through the development process. Again, says Francese, collaboration is essential. “Antibiotics have literally doubled life expectancy. They are a precious resource to be optimally used, not abused, and this is a global problem because bacteria know no borders. “There is a role and responsibility for all of us when it comes to fighting AMR. Local authorities, healthcare systems, national governments, the public and the pharmaceutical industry must all work as a team to tackle AMR.” Written by Linda Whitney
Richard Pickup VP, Environment, Health, Safety, & Sustainability, Teva Pharmaceuticals
© Megan Howe / Mott MacDonald Ltd
Bacteria know no borders – which is why tackling AMR requires global collaboration by pharma companies, governments, healthcare systems and communities.
How to stop a hidden pandemic The UK’s global partnerships are fighting against drug resistance.
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ntimicrobial resistance (AMR) is happening right now across the world. The United Nations and its member countries are committed to ensuring healthy lives for all by 2030. The Sustainable Development Goals depend on us ensuring everyone, everywhere is safe from this threat which does not respect borders. Healthcare for all means healthcare for 7.8 billion people on the planet, so the UK works to ensure that every one of them has access to healthcare, no matter where they live through collaborations and partnerships. Supporting the One Health approach We depend on effective antibiotics for looking after people, animals and the planet. COVID-19 and Ebola exemplify how diseases travel between species and why we need appropriate treatments for each sector. The UK supports a One Health approach, working across human, environmental, animal and fish health.
WRITTEN BY
Professor Dame Sally Davies UK Special Envoy, Antimicrobial Resistance
running water, to installing pioneering equipment– including mass spectrometers to identify bacteria in just two minutes. Targeted training, with expertise from leading UK and international institutions, is building the capacity of laboratory staff to support the health of the most vulnerable around the world. Encouraging global collaboration Our global partnerships are across sectors, as well as countries. We are helping institutional and private investors to understand why AMR matters to us all and how they can put global health at the heart of their investments – achieving sustainable supply chains and the Sustainable Development Goals. We all play a role in tackling AMR AMR will only be solved by looking outwardly, working globally and sharing expertise. The UK supports the World Health Organization, Food and Agriculture Organization, and the Organisation for Animal Health to advance a shared global vision and actions for addressing AMR. Everyone can work together to address AMR. From washing your hands to handling antibiotics with care, we can protect our antimicrobials and our world. With every single one of our international partners and friends, the UK hopes to strengthen global health security for all, for good.
AMR will only be solved by looking outwardly, working globally and sharing expertise.
Data enables evidenced based decisions When high-quality data is produced and shared locally, nationally and globally, then decision-makers can act on them. The UK government’s Fleming Fund is a £265million UK Aid programme supporting countries to collect and use AMR data effectively. Around the world, we are bringing evidence and people together to optimise antimicrobial usage for the long-term and prepare for future challenges. We can use our collaboration to ensure we help support countries and strengthen systems. This includes ensuring labs have access to clean
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Does nature hold the key to a future free of AMR? The power of natural viruses in fighting harmful bacteria in humans and animals can finally be harnessed thanks to new technological advances.
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INTERVIEW WITH
David Browning Chief Executive Officer, Fixed Phage
Written by: Ailsa Colquhoun
Paid for by Fixed Phage
hages have been around for billions of years – well before humans first stepped on the earth – and they are everywhere. On each of your hands there are trillions of these microscopic entities, keeping the bacteria on skin in balance. In the human body, phages outnumber bacteria by 10 to one. They are vital in preserving a healthy ecosystem and every two days, half of the bacteria on the planet are killed by phages. If a bacterial infection occurs, a phage treatment can target a bacterial strain, repeatedly attacking it until the body’s natural defences take over, to remove the bacteria. Such specificity to a particular microbe, coupled with their abundant supply in nature, has led scientists to explore whether phages will be an alternative to antibiotic drugs. Stability concerns addressed Phages were first discovered in 1915
and today, are primarily used in nontherapeutic applications, including reducing food waste and improving animal health - also key areas of focus for Fixed Phage. However, in human and veterinary medicine, where drugs need to be more extensively trialled, phages have not moved into general use. David Browning, CEO of phage development company Fixed Phage, explains: “In their natural state phages are very fragile and they can disappear easily.” Fixed Phage is now commercialising technology that irreversibly binds phages to almost any surface. The immobilisation process delivers phages to targeted locations, extending the antibacterial activity of natural phage from days to years. This could pave the way for phage products to arrive on your pharmacy’s shelf. Alternatives to antibiotics With so few new antimicrobial drugs in the traditional pharma pipeline, policymakers worldwide have begun to look with interest at the use of
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Phages are powerful additions to our antibacterial arsenal, either replacing antibiotics, or being used to extend the lifespan of current/ future antibiotics.” alternative therapies. Dr Jason Clark, Chief Scientific Officer at Fixed Phage, says: “Phages are powerful additions to our antibacterial arsenal, either replacing antibiotics, or being used to extend the lifespan of current/ future antibiotics.” Browning is confident there will be greater use of phage therapy. His view is that the new autonomy that the UK’s regulatory bodies will enjoy will create a more responsive approach to regulatory assessment and approvals for innovative treatments for people and animals. He says: “The scientific community generally accepts that phage therapy is safe because they are widespread in the environment and are specific for their bacterial target. The piece still to be proven, particularly in humans, is effectiveness. As you can imagine, this is a complex process, but things are certainly picking up pace. People are now actively looking at phage as an exciting alternative to antibiotics.”
Read more at fixed-phage.com
The threat of a bacterial pandemic needs a new business model now Bacterial infections could become the next pandemic – and we could be helpless because today’s antibiotic development model is broken.
“T
he World Health Organization (WHO) says 12% of current deaths are due to infections, and an estimated nine different bacteria are developing antimicrobial resistance. By 2050, that could mean 10 million deaths annually at a society cost which could reach $100,000 billion,” says Thierry Mauvernay, President of global biopharmaceutical company Debiopharm. “Unfortunately, the present model of antibiotic development is flawed.”
We need to find new effective antibiotics that work against bacteria resistant to all currently available antibiotics.
Paid for by Debiopharm
Antibiotics are currently not profitable He explains: “Antibiotics typically take an average of 10-12 years to develop and costs are high - between 1 to 2 billion dollars. Meanwhile the purchase price of antibiotics is low, so major pharmaceutical companies have given up on developing new antibiotics because it’s unprofitable.” Therefore, a new business mode is essential.
A new system to incentivise is needed Instead of the pay-per-box system, Mauvernay suggests an insurance system, where manufacturers receive guaranteed payments, whether or not the drugs are used. For instance, for a hospital could pay an annual fee, based on the number of beds, for the right to use a targeted antibiotic. The insurance fees could vary according to the wealth of the country. Alternatively, groups of countries or the WHO could buy the licence. People are starting push for this model, says Mauvernay. New methods to tackling antibiotic resistance bacteria We need to find new effective antibiotics that work against bacteria resistant to all currently available antibiotics, while preserving indigenous gut microbiota. Debiopharm is currently researching into new antibiotics that inhibit the enzyme Fabl, which leads to bacterial cell death. Three of the most dangerous bacteria that affect our society today include Staphylococcus aureus; gonorrhoea; and Acinetobacter, a gram negative bacteria. These three bacteria affect 100
million people annually, but some 10% of these infections are already resistant to any treatment. In some countries, gonorrhoea is resistant to seven of the eight existing treatments. In other countries, Acinetobacter is 100% resistant. We need to continue researching and development new antibiotics for this type of infection, so doctors use nonspecific antibiotics. A new targeted product will prevent AMR.
INTERVIEW WITH
Thierry Mauvernay President, Debiopharm
An estimated nine different bacteria are developing antimicrobial resistance. It’s time to act in partnership “A public-private partnership to co-finance antibiotic development is the solution,” says Mauvernay. “A global research fund of 15 to 20 billion francs over ten years could fund the development of 10 to 20 new classes of antibiotics. At the global level this is a small amount - especially compared with the cost of COVID-19”.
Bertrand Ducrey CEO, Debiopharm
Written by: Linda Whitney
Read more at debiopharm.com
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Diagnostic tests are vital in the fight against antimicrobial resistance The coronavirus pandemic has focussed the world’s attention on the role and importance of diagnostic testing.
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iagnostic tests provide essential data to support treatment decisions; 70% of patient information comes from diagnostic tests. Many tests are done in hospital laboratories, but increasingly technological improvements are enabling access to tests outside traditional settings.
Rapid antimicrobial resistance detection for MDR infections
The need for new diagnostic techniques New infectious diseases diagnostic approaches, increasing the laboratory’s capability for rapid identification and characterisation of pathogens, allow us to define the phenotypic and genotypic characteristics of antimicrobial resistant organisms, in order to ensure optimal impact on the patient management.2 This is particularly important for Gram-negative bacteria (e.g. Enterobacteriaceae). It causes difficult-to-treat infections in both immunosuppressed and hospitalised patients, due to multiple resistance mechanisms contributing to the several observed phenotypes in antibiotic resistant isolates. In some settings, clinicians are normally obliged to treat patients with broad-spectrum antibiotics—even when bacterial infection is microbiologically absent —thereby determining the selection and emergence of antibiotic resistant bacterial organisms. Adopting techniques into decision making process We agree that the new “precision medicine” paradigm—which
Maurizio Sanguinetti Professor of Microbiology, President, European Society of Clinical Microbiology and Infectious Diseases
has extensively been used in cancer chemotherapy—should be ever increasingly applied to antimicrobial chemotherapy.3 Therefore, the information available from rapid diagnostic testing (as for carbapenemase testing) should be immediately incorporated into clinical decision-making pathways regarding the therapy of Gramnegative bacterial BSIs. Specifically, algorithms for the interpretation of AMR testing and treatment of BSIs may be adopted to achieve a rapid, effective and “molecularly-targeted” antimicrobial chemotherapy regimen for any individual patient.4 The use of rapid diagnostic tests for AMR detection will provide critical means to achieve the balance between administration of new and existing antibiotics and emergence of antimicrobial-resistant BSI and notBSI pathogens. Studies that measure the impact of rapid diagnostics-based interventions on both antimicrobial utilisation and time to effective treatment, as well as that determine if use of rapid diagnostics improves BSI patients’ outcomes are urgently needed. References: 1. Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother. 2010;54(11):4851-4863. doi:10.1128/AAC.00627-10 2. Buehler SS, Madison B, Snyder SR, et al. Effectiveness of practices to increase timeliness of providing targeted therapy for inpatients with bloodstream infections: a laboratory medicine best practices systematic review and meta-analysis. Clin Microbiol Rev. 2016;29(1):59-103. doi:10.1128/CMR.00053-14 3. Perez F, El Chakhtoura NG, Papp-Wallace KM, Wilson BM, Bonomo RA. Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply “precision medicine” 4. Giacobbe DR, Giani T, Bassetti M, Marchese A, Viscoli C, Rossolini GM. Rapid microbiological tests for bloodstream infections due to multidrug resistant Gram-negative bacteria: therapeutic implications. Clin Microbiol Infect. 2020;26(6):713-722. doi:10.1016/j.cmi.2019.09.023 ©A N YA I VA N OVA
T
argeting AMR has important clinical implications not only related to diagnosis and management but also prevention of infectious diseases, particularly those causing sepsis. Factors associated with death due to antimicrobial resistant pathogens known as causative agents of community- and hospital- acquired bloodstream infections (BSIs) are not completely elucidated. However, in a meta-analysis of sepsis treatment studies, the mortality rate in patients who were receiving inappropriate empiric antibiotic therapy was higher than among patients who were appropriately treated.1
Doris-Ann Williams MBE Chief Executive, British In Vitro Diagnostics Association
admissions with influenza or pneumonia. Tests can distinguish between a bacterial or viral infection, allowing their symptoms to be treated most appropriately. Critically ill patients with suspected infection need to be tested to diagnose the underlying pathogen, or alternatively to rule-out sepsis which can rapidly become fatal or leave people Keeping the focus on the AMR crisis with life changing damage. Diagnostic testing is also critical to Furthermore, with COVID-19, almost managing antimicrobial resistance all patients admitted to hospital are (AMR). During this year, AMR, like given a five-day course of empiric so many other healthcare issues and antibiotics despite the low incidence diseases, has been overlooked while the of bacterial superinfections. Using global population diagnostic tests gives struggles with the clinicians confidence COVID-19 pandemic. to stop inappropriate Yet AMR remains a antibiotics much global health disaster Tests can distinguish between earlier, helping the that is already killing fight against AMR. a bacterial or viral infection, 700,000 people a Diagnostic tests allowing their symptoms to be year. It is predicted provide critical treated most appropriately. to cause 10 million pieces of information deaths each year to support patient by 2050 if the current situation is not treatments and to monitor if treatments improved. are effective. While the tests can seem Hence it is vital to remember that simple, there is an entire segment of this huge threat to public health has the life sciences industry concentrating not gone away. We need to reduce the on developing and manufacturing inappropriate use of both antibiotics these tools and the equipment required and antimicrobials, to ensure they to perform them using the latest remain active against pathogens when biotechnology. These are the weapons needed most. we need to deploy on the frontline in this ongoing battle against AMR. Helping to diagnose patients more efficiently Diagnostic testing can play a key role in antibiotic stewardship. For example; managing winter hospital
WRITTEN BY
In the last decades, the problem of antimicrobial resistance (AMR) has reached critical proportions to induce global health authorities to regard AMR as a today’s “serious threat” worldwide.
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Employing the power of the microbiome in the fight against AMR To preserve the utility of antibiotics, the world needs to change its approach to treating disease. A potential way forward is by harnessing the power of the human microbiome.
Per Falk President, Ferring Pharmaceuticals
Mirjam Mol-Arts Chief Science and Medical Officer, Ferring Pharmaceuticals
Written by: Tony Greenway
Paid for by Ferring Pharmaceuticals
I
t’s all so depressingly predictable, says Per Falk, President of biopharma company Ferring Pharmaceuticals. Mankind has misused — and overused — life-saving antibiotics, reducing their effectiveness and taking us to the brink of potential medical disaster. The effects of antibiotic misuse “This isn’t a new concern,” explains Falk. “Alexander Fleming, who discovered penicillin, warned about antibiotic resistance in his Nobel prize acceptance speech in the mid-1940s.” “The fact is that bacteria have a tendency to adapt very quickly,” explains Falk. “They change and they learn — but, evidently, we don’t.” “Tragically, the estimate is that by 2050, more people will die of bacterial or other infections than of cancer. That’s a position we haven’t been in for decades.” This is not to say that antibiotics have outlived their usefulness and won’t play a major part in healthcare going forward. On the contrary, they will continue to be lifesavers. “However, we need to use them only when necessary,” stresses Falk. “We must find a way to beat infectious diseases with non-antibiotic treatments, and to reduce the overall antibiotic use in society to maintain their effects when it is needed. It is crucial to ensure their effectiveness long-term to treat potentially deadly and contagious infectious diseases.” The significance of the microbiome That’s why life science players are currently showing enormous interest in the human microbiome, the genome of a complex community of microorganisms which live on every surface of the human body. Scientists have known about the microbiome for over a century but understanding the role it plays in disease has only been possible thanks to technological advances made over the last three decades. Research now shows that the microbiome supports the maintenance and development of the immune system, metabolism, and other functions essential to life. When the microbiome malfunctions, the body’s microbial biology becomes unbalanced with pathogenic bacteria, which can lead to disease. This can include skin diseases such as acne and psoriasis, inflammatory
The estimate is that by 2050, more people will die of bacterial or other infections than of cancer.
©FERRING PHARMACEUTICALS, 2019
INTERVIEW WITH
diseases such as Crohn’s Disease or rheumatoid arthritis, and serious and systemic diseases, such as Clostridioides difficile (C.diff).
But we have to be successful and find a non-antibiotic answer to infection. There is no option not to!” When antibiotics aren’t the answer “Unfortunately, antibiotics can’t be used to treat C.diff completely, because antibiotics are the very drugs that cause it,” Falk points out. Instead, the idea is to use live, lifechanging microbiome therapies to restore a person’s microbial ecology and, ultimately, good health. In simple terms, ‘good’ bacteria are employed to fight ‘bad’ bacteria. “This may be a new and better way to treat infectious disease and so save lives,” says Falk. At present, a microbiome therapy is in late stage clinical development at Ferring, which will hopefully be an effective treatment option for C.diff. However, Mirjam Mol-Arts, Chief Science Officer and Chief Medical
Officer at Ferring Pharmaceuticals, cautions that the science is still in its infancy, and that more work is needed on the regulatory and clinical side to make microbiota-based therapies accessible to patients and physicians. Breakthroughs are possible in the near future The good news is that this area of life science is currently attracting huge venture capital interest. This increases the likelihood that significant and varied microbiome breakthroughs could benefit patients in the next 10 years and avert resistance to life-saving antibiotics. “This is still just the first step,” says Mol-Arts. “But we have to be successful and find a non-antibiotic answer to infection. There is no option not to!” Thankfully, both Falk and Mol-Arts feel as though science is on the cusp of discovery. “In the next few years we’ll see the first microbiome drugs emerging that have been tested and approved according to proper standards,” says Falk. “While Ferring is leading the charge in developing microbiota-based therapeutics, there are three or four companies currently in the race to reach approval. Hopefully more than one of us will succeed. We need different ways of approaching disease to help patients — and there is room for everyone.” Read more at ferring.co.uk
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The threat from antimicrobial resistance remains Now more than ever we must remain united to preserve antimicrobials, particularly as COVID-19 has altered the way many people access healthcare.
WRITTEN BY Dr. Diane Ashiru-oredope Lead Pharmacist, Antimicrobial Resistance and Healthcare Associated Infections Division, National Infection Service, Public Health England (PHE); National Lead, World Antimicrobial Awareness Week (WAAW)
Antimicrobial resistance (AMR) remains a threat to health In 2019 the World Health Organization declared AMR one of the top 10 global health threats facing humanity. Public Health England’s latest English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) report has shown antibiotic resistant bloodstream infections has risen by a third (32%) since 2015 and that antimicrobial resistance is linked to one in five people with key bacterial blood stream infections. Preventing infections and AMR This year, the COVID-19 pandemic has presented numerous additional challenges for health professionals managing patients with infections. Now, more than ever we need to continue to work together to prevent infections – including COVID-19. At the same time, we must continue to make progress in our efforts to tackle antimicrobial resistance through multiple measures, including robust infection prevention and control,
reducing inappropriate antibiotic use, diagnostic stewardship, surveillance. COVID-19 has given us an example of what life without effective treatment for an infection could be. Although a couple of treatment options have been found useful in the management of the infection in hospitalised patients, the best measure for COVID-19 and infections caused by microorganisms resistant to medicines is to prevent the infection in the first instance. Find out how you can protect yourself, your family and friends against the spread of antimicrobial resistance via antibioticguardian.com. COVID-19 and influenza (Flu) The key symptoms of COVID-19 are cough, fever, or loss of, or change in normal sense of smell (anosmia) or taste (ageusia). However, breathlessness, anxiety, delirium and agitation as well as fatigue, muscle aches and headache are also common and similar to other infections (especially flu) and can be difficult to differentiate. It remains critical that individuals with cough, fever, anosmia and ageusia
COVID-19 has given us an example of what life without effective treatment for an infection could be. symptoms and but who are well enough to remain in the community (as well as those caring for them) follow the UK Stay at home guidance and get tested. If the symptoms are mild, people are likely to feel much better in a week. If symptoms get worse, it is important to contact the NHS, for example, NHS 111 online. Whilst there is a vaccine to protect against flu, there is currently no proven vaccine to prevent COVID-19. It is important to continue to follow the current guidance for preventing exposure to the virus with focus on Hands (wash hands regularly), Face (use face coverings) and Space (being mindful of surroundings and keeping 2 metres distance where possible). Read more at globalcause.co.uk