Antibiotic-resistant bacteria kill 25 000 people in the EU every year, and cost the economy €1.5 billion. IMI’s New Drugs 4 Bad Bugs (ND4BB) programme represents an unprecedented partnership between industry, academia and biotech organisations to combat antibiotic resistance in Europe by tackling the scientific, regulatory, and business challenges that are hampering the development of new antibiotics. The programme currently comprises five projects. The COMBACTE project, launched in early 2013, has already established a Europe-wide network of almost 300 clinical and laboratory sites, and will start recruiting patients for clinical trials in 2014.
In its Action Plan against the rising threats from Antimicrobial Resistance of November 2011, the European Commission called for ‘unprecedented collaborate research and development efforts to bring new antibiotics to patients’ by, among other things, launching an IMI programme ‘for research on new antibiotics aimed at improving the efficiency of research and development of new antibiotics through unprecedented open sharing of knowledge’. The result is the New Drugs for Bad Bugs (ND4BB) programme. The first two projects of the programme, COMBACTE and TRANSLOCATION, were launched in early 2013. In addition, three projects are under development, and IMI’s 11th Call for proposals includes a further two indicative topics on AMR.
COMBACTE – creating a pan-European network of clinical sites
COMBACTE was set up with the goal of establishing a pan-European network of excellence of clinical investigation sites to conduct clinical trials enabling the registration of novel agents to treat patients with bacterial infections. Less than a year after its launch, the project has created a network of 293 clinical sites with associated laboratories in 34 countries. The project is also working to improve clinical trial design and in 2014, it will start conducting clinical trials with innovative anti-infectious agents developed by the pharmaceutical companies participating in the project. Ultimately, the networks of clinical centres (Clin-Net), trial laboratories (Lab-Net) and of innovative study design approaches (Statistical Trial and Research Network [STAT-Net]) will become the reference in Europe for the clinical development of new antibiotics.
- Total cost: €195 million
- Project factsheet: COMBACTE-CARE | COMBACTE-MAGNET | COMBACTE-NET
- Project website: https://www.combacte.com/
TRANSLOCATION – getting drugs into bugs (and keeping them there)
TRANSLOCATION started at the same time as COMBACTE and focuses on identifying new ways of getting antibiotics into bacteria and preventing bacteria from expelling the drugs before they can take effect. It will work primarily on Gram-negative pathogens such as Escherichia coli and Klebsiella pneumoniae. Drug-resistant Gram-negative bacteria are responsible for two thirds of the 25 000 deaths resulting from antimicrobial resistance reported in Europe annually. In sharing the knowledge and data discovered, TRANSLOCATION will develop guidelines for designing and developing new drugs to tackle antibiotic resistance and create an information centre for pre-existing and ongoing antibacterial research data which will be used to establish best practices for future antibacterial drug discovery efforts.
- Total cost: €29 million
- Project factsheet: TRANSLOCATION
- Project website: http://www.nd4bb.eu/
A drug-discovery platform for antibiotics
ND4BB Topic 3, launched under IMI’s 8th Call for proposals, will take promising novel molecules identified in the early stages of drug discovery with a view to developing them further into candidate drugs that could be used to treat Gram-negative bacteria, which are particularly difficult to treat. The project offers a unique opportunity for universities and small companies to access the expertise and resources available under a newly-created drug discovery platform to advance their candidate drug molecules. The project is under development and should be launched in early 2014.
- Indicative budget: €85 million
- 8th Call press release
New business models for antibiotic development
ND4BB Topic 4, launched under IMI's 9th Call for proposals, focuses on the urgent need to develop a new business model for antibiotic development that will reinvigorate investments in this vital area while also addressing the issue of the responsible use of antibiotics. The project will have to tackle a contradiction at the heart of antibiotic development: on the one hand, pharmaceutical companies make money by selling large volumes of the drugs they develop. On the other hand, the use of new antibiotics should be restricted, so as to minimise the risk of bacteria developing resistance to them. As a result of this situation, sales are low and the costs of development often exceed the potential return on investment. This new project will develop concrete recommendations for new commercial models that provide industry with an incentive to invest in this area while ensuring that new antibiotics are used wisely. The project is still under development and should be launched in 2014.
- Indicative budget: €9 million
- 9th Call press release: link
Gathering data on the best available treatments
ND4BB Topic 5, also launched under IMI’s 9th Call for proposals, focuses on the clinical development of antibiotics to treat resistant Gram-negative pathogens. This project will aim to gather data on the best-available therapy for hospitalised patients with serious infections caused by multi drug resistant organisms. These data will help to better design clinical studies, thereby increasing the efficiency of antibiotic R&D. This will be tested with a new combination medicine targeting serious Gram-negative infections.
- Indicative budget: €72 million
- 9th Call press release: link
Antimicrobial resistance – a serious threat to health
Antimicrobial resistance (AMR) represents a serious and growing threat to human and animal health worldwide. Resistance can also spread from animals to humans through the food chain or direct contact. According to the World Health Organization (WHO), ‘antibiotic resistance is becoming a public health emergency of yet unknown proportions’. In the EU, AMR is responsible for some 25 000 deaths every year, and the annual treatment and social costs have been estimated at some €1.5 billion (ECDC/EMEA joint technical report The bacterial challenge: time to react, 2009). Meanwhile, new forms of resistance continue to arise and spread, leaving clinicians with few weapons to bring infections under control.
The challenges of antibiotic development
Despite the recognised need for new antibiotics, the reality is that only two new classes of antibiotics have been brought to the market in the last three decades. The reasons for this are manifold. On the scientific front, there is an urgent need for a greater understanding of how antibiotics work, how bacteria develop resistance to them, and what molecular mechanisms could be exploited to get round bacterial defence mechanisms.
Running clinical trials on new antibiotics is also problematic due to regulatory requirements and the large numbers of patients required– put simply, a lot of patients have to be recruited to the major studies of efficacy performed for each clinical indication sought in order to be sure of having enough patients with the resistant bacteria under investigation and to demonstrate that the new antibiotic is not inferior to comparable antibacterial drugs. These issues mean that the costs of carrying out a clinical trial on a new antibiotic are extremely high. At the same time, because some antibiotics will only be used on a very small number of patients, the costs of development often exceed the potential return on investment. In other words, antibiotic development is simply no longer a financially viable option for pharmaceutical companies, and just a handful of pharmaceutical companies remain in the field.
About European Antibiotic Awareness Day
The European Antibiotic Awareness Day is an annual European public health initiative that takes place on 18 November to raise awareness about the threat to public health of antibiotic resistance and prudent antibiotic use. The latest data confirms that across the European Union the number of patients infected by resistant bacteria is increasing and that antibiotic resistance is a major threat to public health. Prudent use of antibiotics can help stop resistant bacteria from developing and help keep antibiotics effective for the use of future generations.
- More information: http://ecdc.europa.eu/en/EAAD/Pages/Home.aspx