The development projects of new antibiotic treatments are falling behind, despite increasing awareness of the antibiotic resistance threat, according to a recently released report by the World Health Organization.
The 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.
Dr Hanan Balkhy ,Assistant Director General on AMR, WHO said that, “The persistent failure to develop, manufacture, and distribute effective new antibiotics is further fueling the impact of antimicrobial resistance (AMR) and threatens our ability to successfully treat bacterial infections.”
All of the new antibiotics released onto the market in the past few decades have been variations of those developed in the 1980s.
The impact of AMR is most severely felt in resource-constrained settings and in vulnerable populations such young children. Bacterial pneumonia and bloodstream infections are some of the major causes of childhood mortality under age 5, and about 30% of neonates with sepsis die due to bacterial infections resistant to multiple first-line antibiotics.
WHO puts out its Antibacterial Pipeline Report every year, reviewing antibiotics under development. 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). Since it began in 2017, this list, which includes 13 priority drug-resistant bacteria, has informed and guided priority areas for research and development.
The 2020 report paints a picture of an almost stalled pipeline with only few antibiotics in recent years receiving regulatory approval. Most of these agents in development have little extra clinical benefit over current ones, with 82% of recently approved antibiotics being derivatives of previous ones with well-established drug-resistance, and drug resistance to these new ones is expected to emerge rapidly.
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”.
Speeding up development requires innovative approaches. For the first time. the 2020 WHO pipeline report includes a comprehensive overview of non-traditional antibacterial medicines, detailing 27 antibacterial agents in the pipeline. These range from antibodies to bacteriophages and therapies that boost the immune response and weaken bacterial effects.
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.
Only a fraction of the promising products in the pipeline will make it to market because of financial and scientific obstacles in the development process.
The preclinical and clinical pipelines continue to be driven by small- and medium-sized companies, which often struggle to finance their products through clinical trials and approval.
The COVID pandemic has deepened the global understanding of the health and economic implications of uncontrolled disease, as well as funding gaps, including investments in R&D of antimicrobial medicines and vaccines, while also demonstrating that much can be achieved with political will and sufficient funding.
“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.”
To address funding challenges in antibiotics development, WHO partnered with the Drugs for Neglected Diseases intitive (DNDi) to set up the Global Antibiotic R&D Partnership (GARDP) to develop promising treatments.
In addition, the WHO has been working closely with other non-profit funding partners such as the CARB-X to “push” and accelerate antibacterial research. Another important new initiative is the AMR Action Fund, a partnership by the European Investment Bank. pharmaceutical companies and philanthropies.