A report by the World Health Organization (WHO) revealed that none of the 43 antibiotics that are currently in clinical development sufficiently address the problem of drug resistance in the world’s most dangerous bacteria.
“The persistent failure to develop, manufacture, and distribute effective new antibiotics is further fuelling the impact of antimicrobial resistance (AMR) and threatens our ability to successfully treat bacterial infections,” said Dr Hanan Balkhy, WHO Assistant Director-General on AMR.
Almost all the new antibiotics that have been brought to market in recent decades are variations of antibiotic drug classes that were discovered by the 1980s.
The impact of AMR is most severe in resource-constrained settings and among vulnerable groups such as newborns and young children. Bacterial pneumonia and bloodstream infections are among the major causes of childhood mortality under the age of five. Approximately 30% of neonates with sepsis die due to bacterial infections resistant to multiple first-line antibiotics.
WHO’s annual Antibacterial Pipeline Report, reviews antibiotics that are in the clinical stages of testing as well as those in early product development. The aim is to assess progress and identify gaps in relation to urgent threats of drug resistance, and to encourage action to fill those gaps.
The report evaluates the potential of the candidates to address the most threatening drug-resistant bacteria outlined in the WHO Bacterial Priority Pathogens List (WHO PPL). This list, which includes 13 priority drug-resistant bacteria, has informed and guided priority areas for research and development since its first publication in 2017.
The 2020 report reveals a near static pipeline with only a few antibiotics being approved by regulatory agencies in recent years. Most of these agents in 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. Therefore, the rapid emergence of drug resistance to these new agents is expected.
The review concludes that “overall, the clinical pipeline and recently approved antibiotics are insufficient to tackle the challenge of increasing emergence and spread of antimicrobial resistance”.
NOVEL SOLUTIONS OUTSIDE THE TRADITIONAL DEVELOPMENT PATHWAY
The lack of progress on antibiotic development highlights the need to explore innovative approaches to treat bacterial infections. 2020 WHO pipeline report for the first time includes a comprehensive overview of non-traditional antibacterial medicines. It highlights 27 non-traditional antibacterial agents in the pipeline ranging from antibodies to bacteriophages and therapies that support the patient’s immune response and weaken the effect of the bacteria.
HIGH FAILURE RATES AND IMPACT ON MARKET DYNAMICS
The report notes that there are some promising products in different stages of development. However, only a fraction of these will ever make it to the market due to the economic and inherent scientific challenges in the drug development process. This, along with the small return on investment from successful antibiotic products, has limited the interest of major private investors and most large pharmaceutical companies.
The report confirms that the preclinical and clinical pipeline continues to be driven by small- and medium-sized companies. These enterprises often struggle to finance their products to the late stages of clinical development or until regulatory approval is obtained.
THE COVID-19 OPPORTUNITY
The Covid-19 crisis has deepened the global understanding of the health and economic implications of an uncontrolled pandemic. It also accentuated the gaps in sustainable funding to address these risks, including investments in R&D of antimicrobial medicines and vaccines, whilst revealing what rapid progress can be made when there is enough political will and enterprise.
“Opportunities emerging from the Covid-19 pandemic must be seized to bring to the forefront the needs for sustainable investments in R&D of new and effective antibiotics,” said Haileyesus Getahun, Director of AMR Global Coordination at WHO. “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.”