Antimicrobial resistance (AMR) is a growing problem worldwide, and with few new drugs making it to the market, there is an urgent need for new medicines to treat resistant infections. The COMBACTE (COMBatting AntimiCrobial resisTance in Europe) project aims to give antibiotic drug development a much-needed boost by pioneering new ways of designing and implementing efficient clinical trials for novel antibiotics. COMBACTE (which started in 2013) is part of the New Drugs for Bad Bugs (ND4BB) programme, tackling AMR and is funded by the Innovative Medicines Initiative (IMI) of the EU.
AMR represents a serious and growing threat to human and animal health worldwide. According to the WHO, ‘antibiotic resistance is becoming a public health emergency of yet unknown proportions’. Meanwhile, new forms of resistance continue to arise and spread, leaving clinicians with few weapons to bring infections under control. Yet 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. If no action is taken to address these issues, we risk leaving society in a situation where doctors will have few, if any, options to treat resistant bacterial infections.
In its Action plan against the rising threats from antimicrobial resistanceof November 2011, the European Commission called for ‘unprecedented collaborative 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 was the New Drugs for Bad Bugs (ND4BB) programme, which includes the COMBACTE project.
COMBACTE – improving clinical trials for antibiotics
The COMBACTE project, with a total budget of more than € 500 million, focuses on addressing the barriers to clinical development. A key objective of the project is developing a high quality, pan-European clinical trial network. Dubbed CLIN-Net, it is capable of recruiting sufficient patients into multinational trials at all stages of development. Alongside this, the project has established a pan-European laboratory network (LAB-Net), which will deliver epidemiological information and data from microbial surveillance work to guide the selection of clinical trial sites. In addition, EPI-Net (focusing on epidemiology) and STAT-Net (focusing on advanced statistics) have been added to the project. Crucially, COMBACTE aims to generate innovative trial designs to facilitate the registration of novel antibacterial agents. It also designs and validates tests to support the diagnosis of patients, identify the most appropriate treatments, and monitor the patient’s response.
The COMBACTE project management office is located at UMC Utrecht, involving approximately 40 people (project managers, investigators, research physicians, clinical trial administrators, data managers, etc.).
Hope for the future
The challenge of antimicrobial development is so great that no organisation could take it on alone. By bringing together leading experts from universities, hospitals, and pharmaceutical companies who are skilled in microbiology, epidemiology, drug development, and clinical trial design, COMBACTE is giving antibiotic development in Europe a major boost. Unique in its scale, ambition, and its potential benefits for patients, public health and pharmaceutical research in Europe, COMBACTE has the potential to become the powerhouse of antimicrobial drug development in Europe, serving as a standard for other groups.
Since the start of COMBACTE in 2013, hundreds of clinical trial sites have taken part in the COMBACTE studies, making possible the enrollment of more than 9,000 patients so far. The project’s overall scientific coordinator, Marc Bonten (professor of medical microbiology at UMC Utrecht), explains the progress so far: “Currently, three COMBACTE studies have completed recruitment and/or data collection, and seven are ongoing. COMBACTE’s network now includes more than 900 clinical trial sites in 42 European countries, and 657 diagnostic labs in 41 countries, making site selection, trial setup and completion faster. In addition, in 2018 COMBACTE has entered an alliance with the Antibacterial Resistance Leadership Group (ARLG), funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. Via this collaboration, US-focused expertise and clinical sites have been added to the programme.”