R&D pipeline grows slightly, with most companies contributing new projects

Promising candidates join pipeline of R&D projects tackling priority pathogens
Eight clinical-stage projects aim to develop completely new treatments

With resistance building and medicines becoming less effective, promising clinical candidates are closely watched to see whether and when they are likely to become available. This section examines how the number of R&D projects targeting priority pathogens has changed since the previous analysis, looking specifically at eight large research-based pharmaceutical companies active in priority pathogens R&D.

Since the previous Benchmark analysis, 22 projects have left the pipeline, for reasons such as project discontinuation or divestment. But there have been 38 additions to the pipeline. Overall, balancing the 22 projects that have left and the 38 additions, the pipeline has seen a modest increase in size: from 77 projects to 92 (net increase of 15 projects).

Although the size of the pipeline overall remains small, this upward movement perhaps signals a stabilisation of activity in this area of R&D by large research-based pharmaceutical companies.

The eight large research-based companies in scope have added 38 new R&D projects to the pipeline since the previous analysis. There are now 92 projects, including some that have recently*** gained marketing approval, targeting the pathogens that pose the greatest risk from antimicrobial resistance.

Furthermore, one third (18) of the 54 projects that remained in the pipeline from the 2020 analysis, have progressed to the next stage of development. Whether an R&D project progresses along the pipeline depends on multiple factors, including the specific disease being targeted as well as other practical challenges.

Of the 38 new projects that entered the pipeline, 25 are innovative medicines and vaccines. These are important because they may constitute new chemical classes of medicines or incorporate new technologies in vaccine development, and such innovations may prove critical in curbing antimicrobial resistance in the years to come.

Eight clinical-stage projects aim to develop completely new treatments

The 2021 Benchmark has identified eight clinical-stage antibacterial and antifungal R&D projects that aim to bring to market new chemical entities or new fixed-drug combinations.

The hope is that such new treatments are sufficiently different from those agents already on the market that pre-existing mechanisms of resistance will not impair their effectiveness. As such, they are some of the most important projects to watch in the antimicrobial pipeline.

These eight projects comprise four antibacterials, two antituberculosis medicines, one antifungal medicine, and one disclosed on condition of confidentiality. Three of them meet some or all of the innovativeness criteria set by WHO to identify candidates with high value to combat resistance, for example because they have a new mechanism of action against the target pathogen.

The remaining five projects, such as fosmanogepix, which potentially represents a new class of antifungal, do not fall within the scope of WHO’s assessment of innovativeness, yet could also provide major therapeutic advances if they reach the market.

The eight projects identified here, if successful, could bolster the antimicrobials arsenal in a few years. Almost all have reached Phase II of development, which is when pharmaceutical companies are expected to start planning how they will bring the new products to people living in low- and middle-income countries, as well as how they plan to safeguard the effectiveness of these medicines with the appropriate stewardship measures.

Looking across all clinical-stage projects, GSK, Otsuka and Pfizer are among the companies that most comprehensively develop such plans.

A closer look at promising candidates

GSK3882347 (GSK)

This non-traditional antibacterial medicine is currently in Phase I. It inhibits the E. coli adhesive protein, FimH, thus preventing infection by impeding the binding of E. coli to the bladder wall. It is indicated for the prevention and/or treatment of UTIs caused by E. coli, part of the Enterobacteriaceae family. Some members of this family are resistant to nearly all antibiotics.

OPC-167832 (Otsuka)

This is a novel carbostyril derivative with antituberculosis activity as a DprE1 inhibitor. This molecule meets all WHO innovativeness criteria. It is currently in Phase II for the treatment of uncomplicated pulmonary tuberculosis in adults.

The table includes two recently approved*** medicines and five innovative medicine candidates in clinical development, from five of the eight companies evaluated. An eighth project is not listed, as it was disclosed on condition of confidentiality.

* Since the previous Benchmark analysis, published in January 2020, which covered projects active between 9 September 2017 and 21 June 2019.

** R&D projects from the nine small and medium-sized enterprises that were also assessed in the previous AMR Benchmark report have been removed from the analysis to allow for comparison.

*** This analysis looks at projects active since 22 June 2019 and up until 30 April 2021.

† The four WHO-defined innovativeness criteria for investigational clinical antibacterial candidates are: new chemical class (or structure); new target; new mode of action; and absence of cross-resistance.