• Today marks an important step forward in the quest for new antibiotics to counter the steady rise of drug-resistant bacteria.

    The Innovative Medicines Initiative (IMI) has launched two new projects under its “New Drugs for Bad Bugs” (ND4BB) programme that will both advance the study of a potential new treatment being developed by AstraZeneca in collaboration with Forest-Cerexa for Gram-negative bacteria, one of the toughest types of “superbugs” to tackle, and articulate the value that new antibiotics can have on society.

    The first new ND4BB project involves a call for academic centers to conduct studies to evaluate Aztreonam-Avibactam (ATM-AVI), including:

    – A Phase IIa pharmacokinetic/pharmacodynamic analysis of ATM-AVI in patients with serious infections caused by Gram-negative pathogens.

    – A Phase III randomised, multicenter, clinical study to evaluate the efficacy and safety of ATM-AVI in the treatment of serious infections caused by Gram-negative pathogens proven or strongly suspected to be caused by multi-drug resistant pathogens.

    Metallo- β-lactamases (MBLs) have emerged in recent years and are a significant risk because MBL-producing bacteria are resistant to the carbapenems, our most reliable and often last-defence class of antibiotics. MBLs pose a particular health threat because of their potential for rapid global spread among bacteria found in both community and hospital settings and because there are currently limited treatment options. Aztreonam’s utility against MBL-producing bacteria  is often limited since the majority of MBL-producing pathogens produce other lactamases that can inactivate aztreonam when it is used on its own.  By combining aztreonam with avibactam, a new β-lactamase inhibitor, we are investigating this combination in patient populations where today there are limited options.

    But how does the broader healthcare community benefit from this research? ………………………………….

    In parallel with the work on ATM-AVI, participating academic centers will collect observational data from their studies which will be made available to all the consortium partners to inform their future clinical development efforts in the hopes that they can progress smaller, less costly clinical development programs to fight multi-drug resistant, Gram-negative superbugs. This provides an important build to the ND4BB programme, which also includes:

    – TRANSLOCATION, a project aimed at increasing the overall understanding of how to get antibiotics into multi-drug resistant Gram-negative bacteria such as Escherichia coli and Klebsiella pneumonia and how to stop the bacteria from ejecting the drug

    – COMBACTE, a project addressing the barriers to clinical development through the establishment of high quality, pan-European clinical trial and laboratory networks and supplemented by a focus on study design and methodology. In COMBACTE there is an additional project aimed at improving clinical development of drugs to treat Gram-positive bacteria and specific focus on a drug from MedImmune, AstraZeneca’s global biologics research arm, for Staphylococcus aureus, the leading cause of antibiotic-resistant healthcare-associated infections worldwide.

    Under the second new ND4BB project, AstraZeneca looks forward to participating in the IMI’s formation of a multi-stakeholder group that will identify new commercial models for antibiotic development. Representatives from academia, industry, venture capital funds, clinical societies, government, payers and patient communities are invited to develop tangible recommendations to spur long term public health policies which encourage stewardship for antibiotics while maintaining meaningful levels of research and development.

    What do economics have to do with antibiotics?…………………………………………………………………………..

    As my colleagues have written in previous LabTalk posts, new antibiotics are hard to discover and hard to develop. But a third and equal challenge is that the economics of delivering new antibiotics to market are not in their favor. The current sales-based reward model for the investment required to create new products is misaligned with the societal need for responsible use. This leads to a current valuation of new agents which do not reflect the true benefit to society and public health priorities. Today’s antibiotics are often generic and relatively inexpensive, which means that the expectation until recently has been that future antibiotics should be similarly priced. Given the dramatic, curative nature of antibiotics and their corresponding societal value of returning years of life, we must create economic incentives for biopharma companies which have limited dollars and whose investors expect a strong return on investment.

    Despite the recognized need for new antimicrobials for clinical use, only two new classes of antibiotics have been brought to market in the last 30 years, and many drug developers have left the field. AstraZeneca invites other pharma and biotech companies to join us in the ND4BB programme to re-create the vibrant, highly competitive R&D environment which produced the antibiotics that are saving patients’ lives today. We welcome the opportunity to work with old and new partners in the search for new drugs for bad bugs.


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