Out of 28 antibiotics in late stages of clinical development, only two have both access and stewardship plans in place
The pipelines captured in the 2018 Benchmark have 175 antimicrobial medicines targeting pathogens seen by WHO and CDC as the biggest AMR threats, including 28 antibiotic candidates in late stages of clinical development. Of these, only two are supported by plans to ensure the successful candidate is both accessible and used wisely.
The pipelines captured in the Benchmark have 175 antimicrobial medicines targeting pathogens seen by WHO and CDC as the biggest AMR threats. Of those, 40 – one quarter – are drug candidates in late stages of clinical development, including 28 antibiotics. Several are novel, with new modes of action, including new classes of antibiotics to treat multidrug-resistant S. aureus. In much of the world, more than half of S. aureus infections are reported to be resistant to standard treatment with methicillin (known as methicillin-resistant S. aureus, or MRSA).
Figure 12. Few late-stage antibiotics with access and stewardship plans.
Once a new antibiotic has market approval, AMR response strategies call for it to be used prudently, to slow the emergence of resistance and maximise the antibiotic’s useful lifespan. Such stewardship measures must be pursued alongside efforts to ensure appropriate access to antimicrobials. More people die from lack of access to antimicrobials than from drug-resistant microbes. Companies must put access and stewardship plans in place at the same time to ensure they are most effective, and before a new product enters the market.
Of the 28 antibiotics in late stages of clinical development, only two (eravacycline, Phase III; bedaquiline for paediatrics, Phase II) have both access and stewardship provisions in place. Eravacycline is being developed by Tetraphase to treat complicated intra-abdominal and urinary tract infections caused by a range of pathogens, including A. baumannii, S. aureus, and C. difficile. To plan for access, Tetraphase is seeking licensing partners to increase access in several regions of the world. For stewardship, it provides hospitals with testing strips that check whether a patient’s infection is susceptible to the drug, which is important to ensure its appropriate use.
Bedaquiline (Sirturo®), conditionally approved for the treatment of multidrug- resistant tuberculosis (MDR-TB) in adults, is now being developed by Johnson & Johnson for the treatment of MDR-TB in children. The company will use the same access and stewardship provisions that are in place for the adult formulation. These include a managed access programme through the Global Drug Facility (GDF) and with its own subsidiaries. To limit resistance to bedaquiline, the company’s stewardship provisions include educational activities for paediatric healthcare professionals that aim to improve knowledge and awareness on the appropriate use of the antibiotic.
Two other antibiotics in the latestage clinical pipeline have stewardship provisions, but no access plan: GSK’s gepotidacin (Phase II) for gonorrhoea; and Pfizer’s avibactam/aztreonam (Phase II) for multidrug-resistant gram-negative bacterial infections. Three have an access plan in place, but no stewardship provisions: a second gonorrhoea medicine, an antibiotic for acute skin infections, and a gel for treating umbilical stump infections (being developed by Entasis, Melinta and GSK respectively).
Besides antibiotics, there are 12 other medicines in late-stage clinical development targeting priority pathogens, including five with both access and stewardship provisions. All are antivirals for HIV/AIDS being developed by GSK, either alone (three) or in partnership with Johnson & Johnson (two).
For a full list of references, please see the 2018 AMR Benchmark report.
A Research & Development
Reporting on companies’ R&D activities to develop new medicines and vaccines that target pathogens posing the greatest threat to human health. This Research Area maps R&D pipelines, highlights areas of focus and where gaps remain, and looks at how companies plan ahead to ensure new products can be rapidly made available for people in need.