Antibacterial products in clinical development for priority pathogens

Published: June 2024

 

WHO analysed the pipeline of antibacterial products (antibiotics and biologicals) that were in phase I-III of clinical development (from 1 July 2017 to 31 December 2023) and which had not, at that date, received market authorization for human use anywhere in the world.

This annual report evaluates whether the current R&D pipeline addresses infections caused by bacterial priority pathogens according to 2024 WHO bacterial priority pathogen list (BPPL), Clostridioides difficile, and Helicobacter pylori. It also evaluates its innovativeness potential and presents trends in research and development (R&D) such as the availability of oral formulation, the range of indications addressed by traditional agents, their spectrum of actions, and the current R&D on paediatric indications and/or formulations.

Candidate products are reported by type, pathogen category, phase of clinical development, expected activity against priority pathogens, route of administration, and innovativeness with a focus on new chemical entities. See below for details on the scope, analysis and limitations. 

 

See also:

 

Health products in the pipeline from discovery to market launch for all diseases
WHO antibacterial preclinical pipeline review
WHO clinical pipeline analysis for antibacterial products, trends from 2017 to current

What you see | Scope, analysis and limitations | Data sources | Previous versions

What you see

The data visualization shows the numbers of antibacterial products by:

  • type (chart A.1), and category of non-traditional products (chart A.2)
  • pathogen category and phase of clinical development (chart A.3)
  • expected activity against priority pathogens (chart B)
  • innovativeness (chart C.1)
  • whether or not a new chemical entity is involved (chart C.2)
  • list of products (by pathogen category and product type) with further information on each product (hover on the phase to open a popup window for additional information) (chart D).
Points to note:
  • As of December 2023, a total of 97 products (57 antibiotics and 40 non-traditional antibacterials; chart A.1) were in clinical development, three of which are in the pre-registration phase. They include:
    -- 32 antibiotics and 30 non-traditional antibacterials targeting WHO bacterial priority pathogens
    -- 19 antibiotics targeting M. tuberculosis (a critical priority pathogen)
    -- 5 antibiotics and 9 non-traditional antibacterials targeting C. difficile, and
    -- 1 antibiotic and 1 non-traditional antibacterial targeting H. pylori
  • Of the 32 antibiotics targeting priority pathogens (click on “Antibiotics” in chart A.1 and “Priority pathogens” in chart A.2):
    -- 18 are expected to have some activity against at least one critical priority pathogen (chart B)
    -- 12 fulfil at least one of the four criteria for innovation (chart C.1)
    -- All 32 antibiotics contain a new chemical entity (chart C.2).
  • Overall, the clinical pipeline and recently approved antibiotics are insufficient to tackle the challenge of increasing emergence and spread of antimicrobial resistance.

To explore the data further

  • Select a product type, pathogen category, pathogen, phase of development or other element – or a combination of elements (e.g., by clicking on a bar in a chart or a cell in a table) – to display the corresponding data in the other charts.
  • Hover the cursor on a bar, a slice in a pie or a cell in a table to see more information in a popup window.
  • Hold the ‘Ctrl’ key on your keyboard to select more than one option.
  • Undo a selection by clicking ‘undo’ or ‘reset’ near the bottom of the page or by clicking the same element again.

Scope, analysis and limitations of the data

Scope

This pipeline analysis focuses on products developed to address drug-resistant infections caused priority pathogen according to the WHO 2024 bacterial priority pathogen list. The data cut-off for the analysis is 31 December 2023 and is limited to products in phases I-III of clinical development that do not have market authorization anywhere in the world and intended for human use. 

The analysis does not include:
-- vaccines;
-- topical decolonizing agents;
-- nonspecific inorganic substances;
-- biodefense agents;
-- agents not developed for systemic use (injectable or oral formulations) or inhalation use, but only for topical application (e.g. creams or eye drops); 
-- new formulations of existing treatments; or

Analysis

  • The analysis was conducted by the WHO Advisory Group on the R&D of Antibacterial Treatments comprised of clinicians, microbiologists, and leading experts in antibiotic R&D, pharmacokinetics/pharmacodynamics (PK/PD) and antibiotic resistance.
  • Products under development were assessed against the available evidence of activity against the priority pathogens according to the WHO bacterial priority pathogen, 2024 update. Assessment for use against OPPs was done for products not active against critical priority pathogens.
  • Products developed against C. difficile and H. pylori were assessed in terms of these pathogens respectively. Their activity was not assessed against the priority pathogens.
  • Four criteria were used to assess if a product could be considered as innovative (at least one should be present):
    -- no (known) cross resistance to existing antibiotics;
    -- new class (scaffold);
    -- new target (new molecular binding site); and/or
    -- new mode of action.

Limitations of the data

The analysis relies on data available in the public domain and input from the WHO Technical Advisory Group on R&D. Some of the products in this analysis are not listed in any clinical trial registry and many registered trials have not disclosed results within the recommended 12 months after completion.

The WHO Secretariat welcomes additional information and/or feedback on the data presented in this analysis. Feedback should be sent to antibacterialpipeline@who.int.