Antibacterial products in clinical development for priority pathogens

Published: November 2019

WHO analysed the pipeline of antibacterial products (antibiotics and biologicals) that were in phase I-III of clinical development (as of September 2019) and which had not, at that date, received market authorization for human use anywhere in the world. The analysis matched the products in development against the WHO priority pathogens list (PPL), Mycobacterium tuberculosis and Clostridium difficile.

Candidate products are reported by type, pathogen category, phase of clinical development, and expected activity against priority pathogens. There is also an assessment of their innovativeness and whether a new chemical entity is involved. The route of administration, antibiotic class and developers are also reported. See below for details on the scope, analysis and limitations.

See also:

What you see | Scope, analysis and limitations | Data sources |  Current version

What you see

The data visualization shows the numbers of antibacterial products by type (chart 1.a), pathogen category and phase of clinical development (chart 1.b), expected activity against priority pathogens (chart 2), innovativeness (chart 3.a) and whether or not a new chemical entity is involved (chart 3.b). Chart 4 lists (by pathogen category) the product type, product name, antibacterial class and phase of clinical developmental of antibacterial products in the pipeline (hover on the phase to open a popup window for additional information, including alternative name, clinical trial registration, product developer, indications and the route of administration).

Points to note:

• As of September 2019, a total of 49 antibiotics and 10 biologicals were in clinical development with (click on each of the pathogen category in chart 1.b and view chart 1a):
  -- 31 antibiotics and 8 biologicals targeting priority pathogens
  -- 12 antibiotics targeting Mycobacterium tuberculosis
  -- 6 antibiotics and 2 biologicals targeting Clostridium difficile
  
• Of the 31 antibiotics targeting priority pathogens (click on “Antibiotics” in chart 1.a and “Priority pathogens” in chart 1.b):
  -- 12 are expected to have some activity against at least one critical gram-negative priority pathogen (chart 2)
  -- 5 fulfil at least one of the four criteria for innovation (chart 3.a)
  -- All 31 antibiotics contain a new chemical entity (chart 3.b)
  
• The biggest gap and need is for innovative antibacterials to treat the priority pathogens, in particular critical gram-negative bacteria

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 the WHO priority pathogen list, Mycobacterium tuberculosis and Clostridium difficile. It covers information available as of September 2019 and is limited to products in phases I-III of clinical development that do not have market authorization anywhere in the world for human use.

The analysis does not include:
-- preventive interventions (such as vaccines or topical decolonizing agents);
-- immunomodulating and microbiome modulating agents;
-- unspecific inorganic substances;
-- biodefense agents;
-- agents not developed for systemic use (injectable or oral formulations), but only for topical application (e.g. creams or eye drops); or
-- new formulations of existing treatments.

Analysis

The analysis was conducted by an advisory group comprised of clinicians, microbiologists, and leading experts in antibiotic R&D, pharmacokinetics/pharmacodynamics (PK/PD) and antibiotic resistance.

Products listed as being developed against critical priority pathogens were only assessed in terms of those critical priority pathogens; they might be active against other priority pathogens (OPP). Assessment for use against OPPs was only done for products not active against critical priority pathogens.

Products developed against Mycobacterium tuberculosis and C. difficile 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):
-- new chemical class;
-- new target or binding site;
-- new mode of action; and/or
-- no cross resistance to other antibiotic classes.

When the advisory group could not reach an agreement on the assessment of innovativeness for some products; these were categorized as ‘inconclusive’.

Data sources