WHO: No antibiotic in development sufficiently addresses drug resistance
None of the 43 traditional antibiotics in the clinical pipeline that target WHO priority pathogens, Clostridioides difficile or tuberculosis sufficiently addresses drug resistance, according to a new report.
WHO’s annual Antibacterial Pipeline Report reviews antibiotic candidates in early development or the clinical stages of testing to assess progress, identify gaps in drug resistance and encourage action to fill those gaps.
This year’s report revealed a “near static” pipeline, WHO said. It outlined 43 traditional antibiotics and combinations in development — 26 that target WHO priority pathogens, 12 that target TB and seven that target C. difficile.
The report states that “antibacterial agents in clinical development unfortunately do not address the problem of extensively or pan-drug-resistant gram-negative bacteria. Novel antibiotics targeting the critical WHO priority pathogens are still lacking.”
“In particular,” the report says, carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa “continue to be insufficiently addressed.” The pipeline also insufficiently addresses oral antibiotic treatment options for extended-spectrum beta-lactamases and carbapenem-resistant Enterobacterales “that could allow treatment outside of a health care facility or shorten the duration of treatment in the facility.”
The report notes that just two new antibiotics for the treatment of multidrug-resistant TB have reached the market in over 70 years, and that investment in research and development for anti-TB agents is at its lowest level since 2008.
According to the report, there are 27 nontraditional antibacterial agents in the clinical pipeline, including nine antibodies, four bacteriophages and phage-derived enzymes, eight microbiome modulating agents, two immunomodulating agents, and four agents in the miscellaneous category that include anti-virulence agents.
Most of the nontraditional products are being tested and are intended for use in combination with standard antibiotics, the report says. Four are in phase 3 development.
Most agents in clinical development “offer limited clinical benefit over existing treatments, with 82% of the recently approved antibiotics being derivatives of existing antibiotic classes with well-established drug resistance,” WHO said.
According to the report, there are more than 290 diverse antibacterial agents in the preclinical pipeline,
“The persistent failure to develop, manufacture and distribute effective new antibiotics is further fueling the impact of antimicrobial resistance and threatens our ability to successfully treat bacterial infections,” Hanan Balkhy, MD, WHO’s Assistant Director General for antimicrobial resistance, said in a press release.
The report also noted that although there are some “promising” products in the pipeline, only a fraction of them will make it to the market because of the economic and scientific challenges in drug development.
“Opportunities emerging from the COVID-19 pandemic must be seized to bring to the forefront the needs for sustainable investments in research and development of new and effective antibiotics,” Haileyesus Getahun, MD, MPH, PhD, who heads WHO’s antimicrobial resistance global coordination efforts, said in the release. “Antibiotics present the Achilles’ heel for universal health coverage and our global health security. We need a global sustained effort, including mechanisms for pooled funding and new and additional investments to meet the magnitude of the AMR threat.”
WHO. 2020 antibacterial agents in clinical and preclinical development: an overview and analysis. https://www.who.int/publications/i/item/9789240021303. Accessed on April 15, 2021.