Very few new antibiotics being developed, even as antibiotic resistance grows – this is signalling a dire public health emergency that needs global coordinated action: CSE

Most big pharmaceutical companies who were developing antibiotics earlier have left the space and are now focussing on more profitable areas like cancer and rare diseases – says CSE’s new assessment   

• Experts at a webinar conducted by CSE highlight how the burden of antibiotic resistance is increasing and existing antibiotics are becoming ineffective
• Most antibiotics developed over the last decade are not novel enough and insufficient to treat multi-drug resistant bacteria
• The global antibiotic pipeline for new antibiotics is weak, particularly against Gram-negative priority pathogens. Short-term scenario is bleak and long-term scenarios lack promise
• Small-and-medium scale antibiotic developers are trying to fill this void but are facing challenges and need support
• Critical reforms are needed to stimulate the antibiotic R&D ecosystem for sustainable and equitable antibiotic access. These reforms include greater public financing, coordinated response from national governments, balanced public-private partnerships in antibiotic R&D
• Considering the dire public-health emergency of AMR, CSE researchers propose that it is time we start thinking if antibiotics can be considered a ‘global public good’  

Find the webinar proceedings click here 

Check Down To Earth’s cover story on the subject click here 

New Delhi, July 30, 2023: According to a World Health Organization (WHO) database, of the 297 antibiotic medicines that are being researched on globally, only 77 are undergoing clinical trials. This is miniscule compared to over 10,000 for cancer, over 1,800 for neuropsychiatric conditions, and about 1,500 for endocrine, blood and immune disorders. 

A webinar conducted recently by Centre for Science and Environment (CSE) has highlighted the dire crisis of research in new antibiotics that the world faces today. Speaking at the webinar, CSE director general Sunita Narain said: “Antibiotics are getting increasingly ineffective. This silent pandemic of antimicrobial resistance is taking lives. What is more frightening is that not only are we not conserving the existing stock of medicines, the drug pipeline for new antibiotics is drying up.” 

“In the years to come we are heading for a triple jeopardy: one, the antibiotics we know today would be increasingly ineffective; two, there would be no new antibiotics available; and, three, there would be a critical need for access to these medicines for all,” Narain added. 

Narain is a member of the Global Leaders Group on Antimicrobial Resistance (AMR), an independent international advisory and advocacy body which has heads of states, ministers and government officials, civil society leaders, and representatives from the private organisations as its members. 

The CSE webinar – titled ‘The Crisis of Antibiotic Research and Development’ -- was the first of a three-part series on the subject. It brought together key stakeholders and experts including James Anderson, executive director, global health, International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), Switzerland; Richard Lawson, senior project manager, Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARBX), USA; Lesley Ogilvie, director of the secretariat, Global AMR R&D Hub, Germany; Amit Khurana, director, Sustainable Food Systems Programme, CSE; and Rajeshwari Sinha, programme manager, Sustainable Food Systems Programme, CSE. Narain moderated the discussions. 

The webinar was based on CSE’s latest assessment – ‘A Developing Crisis’, published in Down To Earth (July 16-31, 2023) magazine. In the assessment, CSE researchers have highlighted how the global antibiotic pipeline is weak across the pre-clinical and clinical development stages. They have analysed the clinical pipeline of 15 high-earning pharmaceutical companies to understand their R&D focus and the role of small and medium pharmaceutical companies. The assessment also covers incentives to support antibiotic R&D and what needs to be done further.  

Speaking at the webinar, Amit Khurana from CSE said: “AMR, antibiotic resistance in particular, is a silent pandemic that is one of the biggest public health threats of current times. The misuse and overuse of antibiotics in humans, animals and crops is making antibiotics ineffective due to growing resistance in bacteria against antibiotics. About five million deaths worldwide were associated with antibiotic resistance in 2019.” 

“Sadly, the antibiotic pipeline has remained stagnant at least 2017 onwards and the short-term and long-term future looks grim. The pipeline is not only weak and fragile but is miniscule compared to pipelines for other diseases like oncology, neuropsychiatry, endocrine, blood and immune disorders. This crisis needs a scaled-up global response,” Khurana added. 

CSE researchers point out that a majority of antibiotic developers are small and medium scale companies. “These companies are struggling and need support,” says Rajeshwari Sinha of CSE. 

“Push incentives have challenges, but they are working. The main limitation of any push funding organisation is that they alone can’t do the job. More money is required but more importantly, coordination and collaboration is the key,” said Richard Lawson of CARBX, which supports small and medium antibiotic developers. 

Lesley Ogilvie of Global AMR R&D Hub pointed out that “despite progress we still have a fragmented pipeline and what we are really lacking is the predictability that would encourage the development of a more sustainable and healthier pipeline. We need to build more robustness and resilience in funding for the antibiotic development pipeline.” 

Talking about the role of big companies, Rajeshwari Sinha said: “Most high-earning companies which were developing antibiotics earlier have exited the space. Only four companies are now developing antibiotics. Almost all are heavily focussed on profitable areas like cancer, which makes it clear that the massive exodus is not just due to the failure of market for antibiotics, often cited by the industry.” 

Acknowledging the crisis with antibiotic R&D, James Anderson from IFPMA said: "Currently, society and healthcare systems place a low value on antibiotics despite the public health risks of AMR, sending a clear signal to companies that investing in them is not a priority. The way to solve this is to improve the conditions through the use of incentives, and the world's leading economies have a role to play in this." 

CSE researchers call for critical reforms to stimulate the antibiotic R&D ecosystem for a sustainable and equitable antibiotic access. There is a need for greater public financing, a coordinated response from national governments and striking the right balance in public-private partnership for antibiotic development. They have highlighted that antibiotics have attributes of a ‘global public good’ despite not fitting into the strictest definition. 

“These life-saving antibiotics must be conserved, which means careful, restricted use, even if less money is made in sales. Access to these medicines is critical to be ensured: drugs will have to be affordable, which also limits the profit interest of pharmaceutical firms. So it is time to look at antibiotics as a global public good,” said Narain as she concluded the webinar. 

Key data findings from the Down To Earth cover story 

Global antibiotic pipeline weak

• WHO database updated until late 2021 shows that of the 297 antibiotic candidates under consideration, 217 are in pre-clinical development, 77 in clinical trial, and only three are in pre-registration stage. This 77 in clinical development is miniscule compared to 10,000+ for cancer, 1800+ for neuropsychiatric conditions and about 1500 for endocrine, blood and immune disorders. 

• Of the 77 products in clinical development, 45 are traditional antibiotic candidates and 32 are non-traditional candidates. Twenty eight out of 45 traditional candidates target WHO priority pathogens. In 2017, 12 pathogens out of which most were Gram-negative were categorised into critical, high and medium priority pathogens to guide global R&D by the WHO. 

• Out of 77, only nine traditional small molecules are in phase three of clinical development. There is none for M tuberculosis. Only two target WHO’s critical priority pathogens. Among the non-traditional antibiotic candidates, only five are in phase three. For M tuberculosis, there is only one product, that too in phase one. 

• The pipeline of antibacterial products in preclinical development shows that out of 217, only three have their Investigative New Drug (IND) application submitted while 31 are in clinical trial application/IND-enabling studies. This is too less a pool to feed into the clinical development stages. 

Big exodus

• Analysis of clinical pipeline of 15 high-earning companies revealed that of the total 1007 candidates, only 13 are antibacterials which are developed by four companies. 400+ were for cancer, about 150 were for immunology, allergy, inflammation or respiratory diseases, and 84 were for cardiology, metabolism or renal. These are developed by most of these companies. Collectively, the 2022 revenue was about US $711 billion, 17.5 per cent of which (US $124 billion) was total investment in research and development. 

• Out of these 15, GlaxoSmithKline, Roche, Pfizer and AbbVie are currently developing antibiotics. GSK is developing eight out of the 13 candidates. Few major companies with clinical pipelines focusing on other profitable areas but not on antibiotics are AstraZeneca, Novartis, Johnson and Johnson, Sanofi, Merck and Co, Bristol-Myers Squibb, Eli Lilly and Company, Gilead Sciences, Amgen, Biogen and Viatris. Sanofi, Pfizer, Johnson and Johnson, Merck and Company and GSK have bacterial vaccines under development. 

For any additional information, please contact Sukanya Nair of The CSE Media Resource Centre, sukanya.nair@cseindia.org, 8816818864.