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Review
. 2024 Aug 7;68(8):e0053524.
doi: 10.1128/aac.00535-24. Epub 2024 Jul 15.

Multi-year analysis of the global preclinical antibacterial pipeline: trends and gaps

Valeria Gigante #  1 , Richard A Alm #  2   3 , Daniela Melchiorri  4 , Tamarie Rocke  3 , Cesar A Arias  5 , Lloyd Czaplewski  6 , Prabhavathi Fernandes  7 , François Franceschi  8 , Stephan Harbarth  9   10 , Roman Kozlov  11 , Christian Lienhardt  12 , Norio Ohmagari  13 , Lesley A Ogilvie  14 , Mical Paul  15   16 , John H Rex  17   18   19   20 , Lynn L Silver  21 , Melvin Spigelman  22 , Hatim Sati  1 , Alexandra M Cameron  1
Affiliations
Review

Multi-year analysis of the global preclinical antibacterial pipeline: trends and gaps

Valeria Gigante et al. Antimicrob Agents Chemother. .

Abstract

Antimicrobial resistance (AMR) is a major global health threat estimated to have caused the deaths of 1.27 million people in 2019, which is more than HIV/AIDS and malaria deaths combined. AMR also has significant consequences on the global economy. If not properly addressed, AMR could immensely impact the world's economy, further increasing the poverty burden in low- and middle-income countries. To mitigate the risk of a post-antibiotic society, where the ability to effectively treat common bacterial infections is being severely threatened, it is necessary to establish a continuous supply of new and novel antibacterial medicines. However, there are gaps in the current pipeline that will prove difficult to address, given the time required to develop new agents. To understand the status of upstream antibiotic development and the challenges faced by drug developers in the early development stage, the World Health Organization has regularly assessed the preclinical and clinical antibacterial development pipeline. The review identifies potential new classes of antibiotics or novel mechanisms of action that can better address resistant bacterial strains. This proactive approach is necessary to stay ahead of evolving resistance patterns and to support the availability of effective treatment options. This review examines the trends in preclinical development and attempts to identify gaps and potential opportunities to overcome the numerous hurdles in the early stages of the antibacterial research and development space.

Keywords: antibiotic; antimicrobial resistance; drug discovery; pipeline.

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Conflict of interest statement

P.F., F.F., V.G., S.H., C.L., N.O., T.R., M.S., L.A.O., D.M., A.M.C., and H.S. declare no conflicts of interest. R.A.A. works for CARB-X. C.A.A. received support from MSD and Entasis in the last 4 years. R.K. provided consultation for MSD and Pfizer between 2016 and 2020. M.P. provided consultation for Shionogi in 2021 and had a grant from Pfizer in 2020. J.H.R. has been chief medical officer and director of F2G, Ltd.; editor-in-chief of AMR.Solutions; operating partner and consultant of Advent Life Sciences; has received grant support from Wellcome Trust; sits on the scientific advisory boards of Bugworks Research, Inc., Basilea Pharmaceutica, Forge Therapeutics, Inc., Novo Holdings, Roche Pharma Research & Early Development, Sumitovant, and the AMR Action Fund; and received consulting fees from Forge Therapeutics, Inc., Innocoll, Vedanta, Progenity, Nosopharm SA, Roivant Sciences, Shionogi Inc., GlaxoSmithKline, and Pfizer Pharmaceuticals. He is currently a shareholder in AstraZeneca Pharmaceuticals, F2G, Ltd, Advent Life Sciences, Zikani Therapeutics, and Bugworks Research, Inc. L.C. is a non-executive director at Curza and has received consulting fees from Clarametyx. He also sat on the Novo Repair Impact Fund SAB. L.L.S. provides consulting and/or scientific advisory board service for Blacksmith, Curza, Techulon, Linnaeus, Prokaryotics, NOVO-REPAIR, IMI-ENABLE, and AMED.

Figures

Fig 1
Fig 1
Total number of preclinical candidates (A) and developers (B) across the four pipeline analyses performed since 2019. 2022 does not appear as the 2021 review was based on 2021 data and was published in 2022. Note: the preclinical pipeline developers include academic institutions, companies, or foundations.
Fig 2
Fig 2
Geographical distribution of the developers with preclinical pipeline projects across the 2019–2023 analysis.
Fig 3
Fig 3
Categorization of developers with preclinical pipeline projects by type (A) and by ownership and size for the commercial companies in 2023 (B).
Fig 4
Fig 4
Distribution of preclinical pipeline projects by biological modality over the last three pipeline reviews. Note: data were available for this analysis from 2020.
Fig 5
Fig 5
Categorization of programs by self-declared stage of preclinical development from 2019 to 2023.
Fig 6
Fig 6
Analysis of narrow-spectrum programs across four consecutive preclinical pipeline reviews. Note: for the sole purpose of this analysis, narrow spectrum refers to agents that target a single species.
Fig 7
Fig 7
Analysis of narrow-spectrum programs by pathogen across four consecutive preclinical pipeline reviews.
Fig 8
Fig 8
Analysis of programs by pathogen across three consecutive preclinical pipeline reviews.
See this image and copyright information in PMC

References

    1. Collaborators AR. 2022. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399:629–655. doi:10.1016/S0140-6736(21)02724-0 - DOI - PMC - PubMed
    1. The World Bank . 2017. Drug-resistant infections: a threat to our economic future. The World Bank/Topics/Health, Geneva, Switzerland. Available from: https://www.worldbank.org/en/topic/health/publication/drug-resistant-inf.... Retrieved 26 Mar 2024.
    1. OECD Publishing . 2023. Embracing a one health framework to fight antimicrobial resistance. OECD Health Policy Studies, Paris, France. Available from: 10.1787/ce44c755-en. Retrieved 26 Mar 2024. - DOI
    1. World Health Organization . 2019. Ten threats to global health in 2019. WHO/Health topics, Geneva, Switzerland. Available from: https://www.who.int/news-room/spotlight/tenthreats-to-global-health-in-2019. Retrieved 26 Mar 2024.
    1. World health organization. 2024. In 2023 Antibacterial agents in clinical and preclinical developmentand. Geneva, Switzerland.

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