WHO's antibacterial pipeline reports

Abstract

Two reports from WHO this year describe the pipeline of antibacterial drugs and vaccines under development to tackle antimicrobial resistance. Vijay Shankar Balakrishnan reports.Research has shown that about 5 million deaths in 2019 were associated with bacterial antimicrobial resistance (AMR) globally. WHO has long recognised the issue, recording World Health Assembly resolutions, securing the AMR Action Fund, and developing a global action plan. To bolster these initiatives, in 2017 WHO came up with a list of bacterial pathogens against which new drugs are urgently needed.Despite this attention from WHO, global pharmaceutical companies focusing on antibiotic development have given up their treasure hunt for new candidates, returning to antimicrobials only because of COVID-19. “The key factor for the companies to leave the antibiotic scene is profit or the lack of it in this case”, said Brian Noonan (Tufts University, Boston, MA, USA), who was with AstraZeneca a decade ago. To Noonan, there are two sub-factors: the timing between medicine administration and cure, and the cost of production versus sale. “Infections tend to be short-term acute diseases: you get sick with pneumonia, take an antibiotic, and you're better in a week”, he said. “Whereas if you have diabetes, Alzheimer's or other diseases, there's a scope for a longer period of sales since you may be taking medicines for a lifetime.” Also, traditionally, antibiotics are relatively inexpensive, making them frivolous candidates for return on investment, Noonan explained.WHO recently released two reports to foster further interest and investment in research and development (R&D) to speed up the fight against AMR: in May, the agency released the antibacterial pipeline report, and in July, the bacterial vaccine pipeline report. The WHO R&D team, including Valeria Gigante and Hatim Sati from the WHO AMR Division and Mateusz Hasso-Agopsowicz and Isabel Frost from the WHO Vaccines Department, came up with the dossier. “Our work is precisely focused on catalysing efforts to address public health priorities, unmet needs and gaps to inform investment in the development of novel antimicrobials, antibacterial vaccines, and diagnostics to address AMR”, Sati told The Lancet Infectious Diseases. “We have done this high-impact research analysis since 2017 when we launched the first WHO list of bacterial priority pathogens for R&D in the context of AMR. The goal of these pipeline analyses and reports is to understand the development landscape of antimicrobials, identify trends, gaps, and opportunities, and to highlight challenges.”The antibacterial pipeline report details preclinical and clinical studies of traditional and novel antibacterial agents worldwide. It offers an assessment of criteria for innovation, such as the known absence of cross-resistance to drugs or new targets or modes of action. The vaccine pipeline report lists 61 vaccine candidates in various stages of clinical development and a further 94 candidates that are in the preclinical stage. It also discusses WHO's position on the science of vaccines and their role in reducing the spread of AMR and saving lives, and the case for new investments.Wendy Thompson (University of Manchester, UK) is a behavioural researcher on antimicrobial overprescribing and antibiotic stewardship in dentistry. Regarding investiments in AMR, she suggests governments should treat AMR R&D as similar to strategic military technologies. “We may or may not end up needing them, but to protect ourselves we need to invest so that the right technology can be deployed quickly when the need arises.”The WHO vaccine pipeline report is a welcome addition to stewardship education and training for Angharad Davies (Royal College of Pathologists, Swansea, UK). “In discussions around AMR, there can tend to be more focus on reducing inappropriate use of antimicrobials than on preventing infections from arising in the first place: vaccination has a crucial but sometimes overlooked role here. The WHO vaccine pipeline report is a very useful resource for educators.”Some experts urge caution regarding the vaccine initiative. Concerns include how to go about addressing vaccine hesitancy and the anti-vaccine movement and the lack of consideration of the impact of antibacterial vaccines on antibiotic stewardship. Timothy Walsh (University of Oxford, UK) said: “We need more information on the vaccination strategy, who will pay for the vaccines, and how these are going to be targeted.” For Tina Joshi (University of Plymouth, UK), “whether new antibiotics or vaccines, if they are going to be expensive, it might discourage low- and middle-income countries from purchasing these [and especially] with vaccines, more research would be necessary to warrant highly specific prophylaxis against hundreds of agents that spur AMR”. For Davies, concerning bacterial vaccines, public acceptance is essential to eventually successfully introduce a vaccine. “It's yet to be seen how the public or specific patient groups will respond to offers of vaccines against pathogens they may not necessarily see as a major threat, such as extra-intestinal pathogenic Escherichia coli, or Klebsiella pneumoniae, for example.”For more on the AMR Action Fund see https://www.amractionfund.com/For the WHO priority pathogens list see https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-neededFor WHO's antibacterial pipeline report see https://www.who.int/publications/i/item/9789240047655For WHO's bacterial vaccine pipeline report see https://www.who.int/publications/i/item/9789240052451 Two reports from WHO this year describe the pipeline of antibacterial drugs and vaccines under development to tackle antimicrobial resistance. Vijay Shankar Balakrishnan reports. Research has shown that about 5 million deaths in 2019 were associated with bacterial antimicrobial resistance (AMR) globally. WHO has long recognised the issue, recording World Health Assembly resolutions, securing the AMR Action Fund, and developing a global action plan. To bolster these initiatives, in 2017 WHO came up with a list of bacterial pathogens against which new drugs are urgently needed. Despite this attention from WHO, global pharmaceutical companies focusing on antibiotic development have given up their treasure hunt for new candidates, returning to antimicrobials only because of COVID-19. “The key factor for the companies to leave the antibiotic scene is profit or the lack of it in this case”, said Brian Noonan (Tufts University, Boston, MA, USA), who was with AstraZeneca a decade ago. To Noonan, there are two sub-factors: the timing between medicine administration and cure, and the cost of production versus sale. “Infections tend to be short-term acute diseases: you get sick with pneumonia, take an antibiotic, and you're better in a week”, he said. “Whereas if you have diabetes, Alzheimer's or other diseases, there's a scope for a longer period of sales since you may be taking medicines for a lifetime.” Also, traditionally, antibiotics are relatively inexpensive, making them frivolous candidates for return on investment, Noonan explained. WHO recently released two reports to foster further interest and investment in research and development (R&D) to speed up the fight against AMR: in May, the agency released the antibacterial pipeline report, and in July, the bacterial vaccine pipeline report. The WHO R&D team, including Valeria Gigante and Hatim Sati from the WHO AMR Division and Mateusz Hasso-Agopsowicz and Isabel Frost from the WHO Vaccines Department, came up with the dossier. “Our work is precisely focused on catalysing efforts to address public health priorities, unmet needs and gaps to inform investment in the development of novel antimicrobials, antibacterial vaccines, and diagnostics to address AMR”, Sati told The Lancet Infectious Diseases. “We have done this high-impact research analysis since 2017 when we launched the first WHO list of bacterial priority pathogens for R&D in the context of AMR. The goal of these pipeline analyses and reports is to understand the development landscape of antimicrobials, identify trends, gaps, and opportunities, and to highlight challenges.” The antibacterial pipeline report details preclinical and clinical studies of traditional and novel antibacterial agents worldwide. It offers an assessment of criteria for innovation, such as the known absence of cross-resistance to drugs or new targets or modes of action. The vaccine pipeline report lists 61 vaccine candidates in various stages of clinical development and a further 94 candidates that are in the preclinical stage. It also discusses WHO's position on the science of vaccines and their role in reducing the spread of AMR and saving lives, and the case for new investments. Wendy Thompson (University of Manchester, UK) is a behavioural researcher on antimicrobial overprescribing and antibiotic stewardship in dentistry. Regarding investiments in AMR, she suggests governments should treat AMR R&D as similar to strategic military technologies. “We may or may not end up needing them, but to protect ourselves we need to invest so that the right technology can be deployed quickly when the need arises.” The WHO vaccine pipeline report is a welcome addition to stewardship education and training for Angharad Davies (Royal College of Pathologists, Swansea, UK). “In discussions around AMR, there can tend to be more focus on reducing inappropriate use of antimicrobials than on preventing infections from arising in the first place: vaccination has a crucial but sometimes overlooked role here. The WHO vaccine pipeline report is a very useful resource for educators.” Some experts urge caution regarding the vaccine initiative. Concerns include how to go about addressing vaccine hesitancy and the anti-vaccine movement and the lack of consideration of the impact of antibacterial vaccines on antibiotic stewardship. Timothy Walsh (University of Oxford, UK) said: “We need more information on the vaccination strategy, who will pay for the vaccines, and how these are going to be targeted.” For Tina Joshi (University of Plymouth, UK), “whether new antibiotics or vaccines, if they are going to be expensive, it might discourage low- and middle-income countries from purchasing these [and especially] with vaccines, more research would be necessary to warrant highly specific prophylaxis against hundreds of agents that spur AMR”. For Davies, concerning bacterial vaccines, public acceptance is essential to eventually successfully introduce a vaccine. “It's yet to be seen how the public or specific patient groups will respond to offers of vaccines against pathogens they may not necessarily see as a major threat, such as extra-intestinal pathogenic Escherichia coli, or Klebsiella pneumoniae, for example.” For more on the AMR Action Fund see https://www.amractionfund.com/For the WHO priority pathogens list see https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-neededFor WHO's antibacterial pipeline report see https://www.who.int/publications/i/item/9789240047655For WHO's bacterial vaccine pipeline report see https://www.who.int/publications/i/item/9789240052451 For more on the AMR Action Fund see https://www.amractionfund.com/For the WHO priority pathogens list see https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-neededFor WHO's antibacterial pipeline report see https://www.who.int/publications/i/item/9789240047655For WHO's bacterial vaccine pipeline report see https://www.who.int/publications/i/item/9789240052451 For more on the AMR Action Fund see https://www.amractionfund.com/ For the WHO priority pathogens list see https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed For WHO's antibacterial pipeline report see https://www.who.int/publications/i/item/9789240047655 For WHO's bacterial vaccine pipeline report see https://www.who.int/publications/i/item/9789240052451