The World Health Organization (WHO) has released the latest report after a gap of two years that shows an analysis of antibacterial agents in clinical and preclinical development. The analysis encompasses traditional and non-traditional antibacterial agents in development globally.
Traditional agents work by directly targeting components essential for bacterial growth or to eliminate the pathogen, while non-traditional agents lack inherent antibacterial properties and achieve their effects through alternative mechanisms.
The report also assesses how well the current pipeline addresses infections caused by drug-resistant bacterial pathogens listed in the 2024 WHO bacterial priority pathogen list (BPP). Drugs targeting drug-resistant Mycobacterium tuberculosis are analyzed separately from those targeting other WHO BPPs, offering an overview of the current research and development landscape and guiding efforts towards addressing critical medical needs.
In addition to the bacterial priority pathogen list, the review covers products designed to combat Clostridioides difficile and Helicobacter pylori, recognizing their clinical significance and associated resistance issues.
According to the report, the current clinical pipeline for antibacterial agents comprises a total of 97 products and/or combinations. Among these, 57 are classified as traditional antibacterial agents, while 40 fall under the category of non-traditional agents. Within the traditional category, 32 agents are aimed at tackling WHO bacterial priority pathogens (BPPs), with an additional 19 targeting drug-resistant M. tuberculosis. Furthermore, development efforts include five agents for C. difficile and one for H. pylori.
Among the non-traditional agents, 30 are specifically targeting WHO BPPs, with nine focused on C. difficile and one designed for H. pylori. These figures underscore ongoing efforts to address critical bacterial infections and combat antimicrobial resistance across different pathogens.
According to the latest analysis from WHO, as of November 2021, there were 80 antibacterial products undergoing clinical development. Of these, 46 were categorized as traditional antibacterials, while 34 were classified as non-traditional. The analysis focused on infections caused by drug-resistant bacterial pathogens listed in the updated WHO priority pathogens list of 2017, including Mycobacterium tuberculosis and Clostridioides difficile.
It’s worth noting that WHO has relied on the 2017 priority pathogen list for previous analyses, but this year’s report incorporates insights from the latest updated list. This update aims to provide a more comprehensive evaluation of current antibacterial pipeline developments.
The report also assessed the progress made in antibiotic development over the past six years, highlighting that while there have been advancements, the collective efforts of clinical-stage antibacterial agents and those approved in recent years still fall short in addressing the escalating threat posed by drug-resistant infections.
In clinical stages, drugs undergo rigorous testing in humans through Phase 1, Phase 2, and Phase 3 trials. These phases evaluate the drug’s safety, effectiveness, dosing, and interactions, starting with small groups of healthy volunteers and progressing to larger patient populations. This critical testing phase aims to ensure that new antibacterial treatments meet stringent regulatory standards before they can be approved for widespread use.
Before the tests are conducted on Humans, the antibiotics have to go through firstly, the drug discovery stage which includes selecting and optimising antibiotic leads after that comes the pre-clinical stage where the evaluation of antibiotic candidates for safety and efficacy in animals has been completed.
According to the report, there are currently 244 products in preclinical development targeting the WHO 2023 bacterial priority pathogen list and C. difficile. In comparison, the previous analysis released in 2022 identified 217 antibacterial products in preclinical stages.
Of the developers involved in the preclinical pipeline, 95% are categorized as micro, small, and medium-sized enterprises. This trend continues to reflect the ongoing pattern observed in previous years, where a significant majority of preclinical pipeline developers are small, privately funded organizations. This also underscores the notable absence of large pharmaceutical companies actively engaging in antibiotic discovery.
In a related assessment published last year by researchers from Delhi-based think tank Centre for Science and Environment (CSE) in the July 16-31, 2023 edition of Down To Earth magazine, the global antibiotic pipeline was described as fragile and lacking robustness. The article emphasized the departure of major pharmaceutical firms from antibiotic development, once the forefront of innovation in this field.
The 2023 analysis also identified 62 programs (25.4%) that are currently in the investigational new drug (IND)–enabling phase of preclinical development. This stage represents the final step before a drug can enter clinical trials. This figure marks a notable increase compared to previous pipeline reports, with the 2022 analysis noting only 34 programs in the IND-enabling stage.
“Antimicrobial resistance is only getting worse. Yet, we’re not developing new trailblazing products fast enough to combat the most dangerous and deadly bacteria,” said Yukiko Nakatani, WHO’s assistant director-general for antimicrobial resistance, ad interim, in the press release for the report. “Innovation is badly lacking yet, even when new products are authorised, access is a serious challenge. Antibacterial agents are simply not reaching the patients who desperately need them, in countries of all income levels,” added Yukiko.
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