Zosurabalpin, a novel antibiotic currently in Phase I development by Roche, has recently showed promise in ending a 50-year drought in effective treatment against carbapenem-resistant Acinetobacter Baumanni (CRAB), which is categorized by the World Health Organisation (WHO) as a “priority 1 pathogen.” Demonstrating efficacy in vitro and in mouse models, zosurabalpin targets a critical bacterial protein complex, offering a new approach in the battle against antimicrobial resistance (AMR) and potentially life-threatening hospital infections, says GlobalData, a leading data and analytics company.

Anaelle Tannen, Infectious Disease Analyst at GlobalData, comments: “CRAB is known to be a very difficult bacterium to defeat, particularly because of its double lipopolysaccharide (LPS) outer membrane, which provides a protective layer against antibiotic treatment. Consequently, invasive CRAB infections can lead to mortality in up to 60% of cases, demonstrating the high level of unmet need in this indication. While zosurabalpin is only at an early stage of clinical development, these positive data represent an incredible step towards better available therapeutics for this type of infection.”

Zosurabalpin functions by inhibiting a bacterial protein complex called LptB2FGC. This blocks the LPS from being transported to the surface of the bacterium. Instead, the LPS builds up to toxic levels within the microbe which leads to its eventual death.

Tannen adds: “Zosurabalpin is a new molecular entity which has the potential to treat lethal hospital infections through its unique mechanism of action. It is also possible that this framework, of targeting the LPS outer membrane, could be utilized for the treatment of various other bacterial infections and thus this discovery could be revolutionary.

Besides zosurabalpin, there are nine other drugs currently in clinical development for the treatment of acinetobacter infections, according to GlobalData. Examples include Fetroja (cefiderocol sulfate tosylate), which is already marketed for the treatment of urinary tract infections and hospital acquired pneumonia, amongst other infections, and is currently in late-stage development for acinetobacter infections in the US, EU and Japan.

However, the overall pipeline is small and with only eight clinical trials currently ongoing or planned for this indication there is limited activity in this space, particularly considering the very high level of unmet need.

Tannen concludes: “The discovery of zosurabalpin could help in the fight against AMR, with the possibility of saving countless lives upon its success in clinical trials.”