Antibiotics in clinical development

Critical analysis of antibacterial agents in clinical development

Nature Reviews Microbiology (2020)

In this new publication I analysed the antibiotics in clinical development. A special focus was placed on bacteriological aspects and the ability of the antibiotics to potentially treat the WHO critical priority pathogens. The article is intended as an  addition to the recent WHO clinical pipeline report that focused on the analysis of the pipeline.

Preclinical antibacterial pipeline

The global preclinical antibacterial pipeline is characterized by a high level of diversity and interesting scientific concepts, although this innovative potential does not necessarily solve the most critical therapeutic problems and may not translate to relevant clinical effects. This analysis of 407 projects from 314 insti-tutions is the first study to provide a snapshot of the current global preclinical activities. More here…

 

Non-traditional antibacterial therapeutic options and challenges

This review summarizes the progress and setbacks of non-traditional approaches. The development of non-traditional treatments suffers similar challenges faced by developers of conventional antibiotics; however, most of these new strategies have additional and considerable hurdles before it can be shown that they are safe and provide a meaningful clinical benefit to patients. While there is a considerable interest in the opportunities that non-traditional approaches will bring to treating bacterial infections, it is likely that effective treatments will be limited to healthcare settings with the best diagnostic and financial resources and healthcare systems that are able to financially support a strong growth of high-cost individual (personalized) medicines and thus to high-income countries.

Non-traditional Antibacterial Therapeutic Options and Challenges. Theuretzbacher U, Piddock LJV. Cell Host Microbe. 2019, 26(1):61-72.

Analysis of the clinical antibacterial drug pipeline

The clinical antibacterial pipeline is dominated by derivatives of established classes and most development candidates display limited innovation. New antibacterial drugs without pre-existing cross-resistance are under-represented and are urgently needed, especially for geographical regions with high resistance rates among Gram-negative bacteria and M tuberculosis.

This  comprehensive analysis of the global clinical pipeline of antibacterial
drugs presents a catalogue of all antibacterial drugs in clinical development and assesses both their potential activity against the WHO critical priority pathogens for R&D (including Mycobacterium
tuberculosis and Clostridium difficile) as well as their degree of
innovation. This analysis focuses on the assessment of the pipeline against global public health needs, its potential innovation, and clinical value globally.

Analysis of the clinical antibacterial and antituberculosis pipeline.

Theuretzbacher U, Gottwalt S, Beyer P, Butler M, Czaplewski L, Lienhardt C, Moja L, Paul M, Paulin S, Rex JH, Silver LL, Spigelman M, Thwaites GE, Paccaud JP, Harbarth S. Lancet Infect Dis. 2019 Feb;19(2):e40-e50.

Tables

WHO priority pathogen list for R&D published

The WHO priority pathogen list for R&D was recently published. I contributed my R&D expertise to this intense work. The list should prioritise and guide R&D of new antibiotics, as part of WHO’s efforts to address growing global resistance to antimicrobial drugs. The process was based on collecting all available evidence to develop criteria that were used in a multi-criteria decision analysis technique vetted by a group of international experts.

The list is an important step to spur governments to put in place policies that incentivize basic science and R&D by both publicly funded agencies and the private sector investing in new antibiotic discovery.

List

Antibacterial innovation in European SMEs

This analysis provides a current snapshot of the innovation potential for antibacterial R&D among European small and medium-sized enterprises (SMEs). It has been recently published in Nature Reviews Drug Discovery. The report shows that far more effective coordination and well-targeted support by public and philanthropic funders will be crucial to sufficiently fill antibiotic R&D pipelines according to priorities based on the greatest public health needs.

Ursula Theuretzbacher: Antibacterial innovation in European SMEs. Nature Reviews Drug Discovery 2016, 15:812–813

Council of the European Union: Next steps to combat antimicrobial resistance

On 17 June, 2016, the Council of the European Union published conclusions on the next steps for the EU to combat antimicrobial resistance (AMR) under a One Health approach. The role of the Council is to serve as the voice of the EU member governments. The Council welcomes other international and regional initiatives, such as the declaration by the G7 on Antimicrobial Resistance and the decision to put antimicrobial resistance on the agenda of the G20.

In its conclusions to combat AMR, the Council has adopted a One Health approach, which considers the importance of intricate interactions between human, animal, and environmental health in addressing AMR. The conclusions also state the importance of research and development into new antimicrobials, as evidenced by item 16 below, where the Council recognizes the accomplishments of DRIVE-AB in this area:

16. UNDERLINES that in order to stimulate the development of new antimicrobials, alternative therapies and (rapid) diagnostics, EU and global coordination and cooperation on research programmes and incentives are needed and RECOGNISES the work done by the Innovative Medicines Initiative (IMI) project DRIVE-AB (Driving reinvestment in research and development and responsible antibiotic use), the proposals of the Antimicrobial Resistance Review team and the Joint Programming Initiative on Antimicrobial Resistance among others.

DRIVE-AB is a publi-private-partnership supported by the the Innovative Medicines Initiative of the EU and developes new economoic models to stimulate antibiotic R&D.

Conference to stimulate innovation in antibiotic R&D

On Thursday 2 June, 2016, the DRIVE-AB consortium, which is developing new economic models to stimulate antibiotic innovation and ensure global access to and sustainable use of antibiotics, held the “Stimulating innovation, sustainable use and global access to antibiotics” conference in Amsterdam.

Global leaders agree on the need to maintain a steady supply of new antibiotics for all as a critical part of the strategy to address antibiotic resistance and that new reward models are necessary to achieve this goal. While basic frameworks have been proposed, the DRIVE-AB consortium seeks a level of granularity that other initiatives have not, moving beyond discussions to concrete plans for policy implementation.

DRIVE-AB shared its preliminary proposals at the event, which attracted more than 180 high-level decision-makers and policy experts, economists, regulatory and public health experts and representatives of pharmaceutical companies and research institutions from around the world. The conference featured keynote speakers and panellists from the World Health Organization, the European Commission, the European Investment Bank, and the US Centers for Disease Control and Prevention, to name a few. The participation of a diverse group of stakeholders at the conference illustrates the level of global interest in the outcomes of DRIVE-AB, and will help the consortium secure the buy-in of stakeholders who can help to implement new incentive policies.

More….

DRIVE-AB Conference in Amsterdam

The DRIVE-AB Conference Stimulating innovation, sustainable use and global access to antibiotics will take place on 2 and 3 June 2016 in Amsterdam. This conference, generously funded by the Government of the Netherlands and organized by the IMI DRIVE AB consortium, will bring together about 150 invited decision-makers and policy influencers from around the world to explore current and proposed efforts to address antibiotic resistance. The main goal of the meeting is to move beyond discussions and instead identify key policies that can be implemented globally to both stimulate the innovation of critically-needed new treatments and ensure their availability and responsible use. Input from the conference will help inform DRIVE AB’s policy recommendations to the European Commission—an important part of growing global discussion on how to manage the looming public health threat of resistance.

Presenting at TATFAR meeting in Luxembourg

The Transatlantic Taskforce on Antimicrobial Resistance (TATFAR) identifies and adopts recommendations for collaborations between the US and the EU to respond to the growing challenges posed by antimicrobial resistance. The biennial in-person TATFAR meeting will take place October 22-23, 2015 in Luxembourg City and I have been invited to present my views in the expert workshop “How do we keep new antibiotics effective? Balancing access and conservation”.

My slides will be available on the AIDA website after the meeting.