The WHO has reiterated the urgent need for new antibiotics, saying the number of antibacterial agents in preclinical and clinical development worldwide increased from 80 to 97 from 2021 to 2023 and that new drugs are crucial to combat severe infections and those tied to antimicrobial resistance (AMR).
In a report released last week – the first published since 2017 – the agency assesses whether antibiotics in the pipeline are likely to deal with infections caused by WHO priority pathogens, which are drug-resistant bacteria posing the greatest risk to human health.
Dr Yukiko Nakatani, interim WHO assistant director-general for antimicrobial resistance, said antimicrobial resistance is getting worse, CIDRAP reports.
“And yet, we’re not developing new trailblazing products fast enough to combat the most dangerous and deadly bacteria. Innovation is badly lacking and even when new products are authorised, access is a serious challenge.”
Gaps across the pipeline
Thirteen antimicrobials have been authorised by the US Food and Drug Administration, the European Medicines Agency, or other stringent regulatory organisation since July 2017, the report said.
But only two are in a new chemical class and considered innovative, which the authors said highlights the challenges of discovering new effective and safe antibacterials.
Three non-traditional drugs to restore gut microbiota in adults have also been authorised to prevent recurrent Clostridioides difficile infection (CDI) after antibiotic treatment.
Of the 97 in-development antibiotics, 57 are traditional antibacterials, including 12 new products that have entered the pipeline since 2017. Of the 57 traditional antibiotics, 56% are intended for use against highest-risk WHO priority pathogens (eg, Acinetobacter baumannii, carbapenem-resistant Enterobacterales), and 33% are designed to combat drug-resistant Mycobacterium tuberculosis.
Also, five traditional drugs (9%) are being developed against CDI, and one targets Heliobacter pylori.
Of the 32 in-development antibiotics against bacterial priority pathogens, only 12 are considered innovative, and only four of the 12 are active against at least one WHO critical pathogen included in the highest-risk category.
The antibiotic-development pipeline is lacking medications for children, convenient oral formulations for non-hospitalised patients, and drugs designed to fight drug resistance, the authors said.
Of the 40 non-traditional antibiotics, 30 are intended against WHO critical high-priority pathogens, nine are directed against CDI, and one targets H pylori.
Need for greater collaboration, access
While progress is being made in non-traditional drugs like bacteriophages, antibodies, anti-virulence agents, immune-modulating drugs, and microbiome-modulating agents, further research is needed to determine how they can be used in the clinical setting.
The preclinical pipeline is more active and innovative, the report said, with many non-traditional drugs and a continued focus on gram-negative bacteria that are resistant to last-resort antibiotics. But the development of antibiotics targeting a single type of bacteria has levelled off.
These drugs, the report said, require broadly available and affordable rapid tests to confirm that the target bacteria are present.
The authors called for greater transparency into the pipeline to enable collaboration on challenging projects, help researchers and drug developers, and interest potential funders. The resulting drugs need to be accessible to all, especially those in low- and middle-income countries, they added.
“Policy efforts on R&D and use should focus on financial and non-financial incentives and efforts to optimise the use of authorised antibiotics, develop novel antibacterial agents and explore new fixed-dose combinations of antibiotics for treating serious bacterial infections like neonatal sepsis,” the researchers wrote.
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