Antibacterial products in clinical development for priority pathogens
Published: September 2017
WHO analysed the pipeline of antibacterial products (antibiotics and biologicals) that were in phase I-III of clinical development (as of May 2017) 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.
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 May 2017, a total of 51 antibiotics (including combinations) and 11 biologicals are in clinical development (chart 1.a), with 46, 7 and 9 respectively addressing the WHO priority pathogens, Mycobacterium tuberculosis and Clostridium difficile (chart 1.b).
- Across all products, 28, 20 and 14 are in phase I, II and III of clinical development respectively (chart 1.b).
- Of the 46 products that target the WHO priority pathogens (click on ‘priority pathogens’ in chart 1.b), 42 are new chemical entities (chart 3.b). Of these new chemical entities, 33 are antibiotics and 9 are biologicals (click on ‘42’ in chart 3.b and then view chart 1.a). Seven of the 33 antibiotics are considered innovative (chart 3.a).
- Chart 2 shows the number of products expected to be active, possibly active or not active against the WHO priority pathogens (click on any number, except totals or subtotals, in chart 2 to filter for the relevant products in chart 4 plus further pertinent information in the other charts). Note: One product can target more than one pathogen; hence, the total number of products in chart 2 is higher than the total number of products in the other charts. To see how many pathogens a product may target, click on a product name in chart 4 and then view information in chart 2.
- Among the seven antibiotics to address resistance against Mycobacterium tuberculosis (click on Mycobacterium tuberculosis in chart 1.b to filter), only one is in phase III of clinical development (chart 1.b) and five are innovative (chart 3.a). All seven are new chemical entities (chart 3.b).
- Seven antibiotics and two biologicals are being developed against C. difficile (click on this pathogen in chart 1.b to filter). Among these, three products are innovative (chart 3.a) and all nine are new chemical entities (chart 3.b).
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
- 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 1 May 2017 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.
- 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’.
Limitations of the data
- Some of the products in this analysis are not listed in any clinical trial registry and the majority of trials have not disclosed results within the recommended 12 months after completion.
- Knowledge of drug development projects, especially for early stage products, relies to a certain extent on informal information by experts familiar with this field, including from presentations and posters at scientific conferences or business meetings. Such projects were considered in this analysis when information about them was also publicly available.
- Primary assessment was based on in-vitro data with some secondary data on PK/PD and clinical information when available.