Which pathogens are receiving most attention in R&D?

• Six of the eight companies in scope are targeting pathogens in the highest threat categories use by WHO and the US CDC, including 18 projects in clinical-stage development or recently approved

• Six of the companies evaluated are developing vaccines (30) for the pathogens in scope.

The 2021 Antimicrobial Resistance Benchmark examines the antibacterial and antifungal pipelines of eight large research-based pharmaceutical companies. By volume and value of sales, these are the largest players in the global market for antibacterial medicines that are active in innovative R&D today. The aim is to capture how these companies are supporting global efforts to replenish and protect the antimicrobial pipeline.

The Benchmark focuses on R&D projects that target the priority bacteria and fungi identified by WHO2 and the CDC as being of particular concern due to drug resistance, for which there is an urgent global need for new treatments. Collectively, the eight companies evaluated have 92 R&D projects in the R&D pipeline that target these 'priority pathogens'. 

Are projects targeting the most critical and urgent pathogens?

There are three levels of prioritisation in the WHO priority list: critical, high, and medium, and four levels of threat in the CDC list: urgent, serious, concerning and watch. Six of the pathogens fall into one or other of these prioritisation categories, including Candida auris, one of only two fungal pathogens on either list. Many strains of C.auris are proving resistant to all three existing classes of antifungal medicines.

The pathogens targeted most frequently by the eight companies are: CR-/ESBL producing Enterobacteriaceae (14 unique products) and P. aeruginosa (8 unique products). Within the Enterobacteriaceae family, the focus is on E. coli and Klebsiella pneumoniae.

GSK leads in this area followed by Pfizer and Shionogi. These three companies have increased the number of their projects targeting critical and urgent priorities since the last iteration of the AMR Benchmark. 

Three companies are developing vaccines targeting pathogens categorised as critical and/or urgent: GSK (C. difficile and N. gonorrhoea), Johnson & Johnson (E. coli) and Pfizer (C.difficile). 

Few vaccine projects for gram-negative pathogens

Approximately one third of the pipeline comprises vaccine R&D projects. Vaccines are a critical tool for preventing the spread of infectious diseases, and
thereby the development and spread of AMR. Overall, S. pneumoniae followed by Enterobacteriaceae are targeted by most vaccine candidates in the pipeline.

However, very few vaccine candidates target other gram-negative pathogens in scope. This leaves some concerning gaps, such as for A. baumannii, an opportunistic pathogen that is associated with hospital outbreaks, as well as for P. aeruginosa. Both placed by WHO and CDC in the highest risk categories.

Six of the companies evaluated are developing vaccines (30) for the pathogens in scope. Shionogi is new to this group in 2021, having entered a collaboration with HanaVax to develop a vaccine against S. pneumoniae. GSK is developing 16 vaccines, more than any other company. 

It is followed by Pfizer, with four. Both have clinical-stage vaccine candidates targeting C. difficile. These are the only clinical-stage vaccine candidates, alongside GSK’s Bexsero (targeting N. gonorrhoeae) and Johnson & Johnson’s ExPEC9V vaccine (targeting E. coli), these C. difficile vaccines, targeting pathogens in the critical and/or urgent categories. 

Promising candidates

PFIZER
C. difficile vaccine (PF-06425090)
Phase III

This innovative vaccine in Phase III would represent the first available vaccine against C. difficile, a pathogen categorised as an urgent threat by the CDC. This pathogen causes diarrhoeal disease. Severe, life-threatening cases present mostly in older patients. 

Stewardship & Access plan: Assuming regulatory and clinical success, Pfizer would seek to register the product in countries with the highest local burden of disease and explore equitable pricing strategies. Given the lack of data in many countries, particularly LMICs, Pfizer is conducting real world data research studies in several LMICs to strengthen its understanding of burden and unmet need and better assess current burden of disease.

GSK
M. Tuberculosis prophylactic vaccine M72/AS01E (GSK692342)
Phase II

This innovative vaccine currently in Phase II trials shows up to 50% efficacy in the prevention of tuberculosis in adults, which is high compared to rates achieved by other candidates.

Access plan: In 2020, GSK licensed the vaccine to the Bill & Melinda Gates Medical Research Institute (Gates MRI). The Gates MRI now leads the candidate development and will sponsor future clinical trials, while GSK will provide the AS01 adjuvant. This agreement increases the likelihood that the candidate is optimised for use in low-income countries and that it is available shortly after approval in countries with a high burden of tuberculosis.