Could novel antibiotic successfully treat a ‘priority 1 pathogen’?

According to GlobalData, with demonstrated efficacy against carbapenem-resistant Acinetobacter Baumanni (CRAB), Roche’s zosurabalpin “has the potential to treat lethal hospital infection,” Anaelle Tannen, Infectious Disease Analyst at GlobalData explained. Currently in Phase I development, the antibiotic’s novel mechanism of action was showcased through its effectiveness against the pathogen in in vitro studies.

If future development is successful, the drug could present a new approach to overcoming antimicrobial resistance (AMR), GlobalData suggested.

Targeting a priority 1 pathogen

GlobalData highlighted that CRAB is “priority 1 pathogen”, as categorised by the World Health Organisation (WHO). According to a 2023 paper published in The Lancet, CRAB is a “Gram-negative coccobacillus that causes severe disease including pneumonia, urinary tract infection, bacteraemia, meningitis, or skin and soft tissue infections, particularly in hospitalised patients.”

“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 percent 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,” Tannen shared.

Targeting the LPS outer membrane could be an approach used for treating other bacterial infections; “thus this discovery could be revolutionary,” Tannen asserted.

Zosurabalpin inhibits the bacterial protein complex LptB2FGC, resulting in the LPS reaching a toxic level within the microbe, causing it to die, the analytics company noted.

Clinical development landscape for acinetobacter infection treatments

Advancing antibiotic drugs

GlobalData highlighted that nine other drugs, alongside zosurabalpin, are in clinical development for treating acinetobacter infections.

An example is Fetroja (cefiderocol sulfate tosylate). Although it is currently in late-stage development for acinetobacter infections in the US, EU and Japan, the medicine is currently marketed for infections such as urinary tract infections, GlobalData added.

The company also shared that overall, there are only eight clinical trials ongoing or planned for this indication, which is important to note, considering there is a “very high level of unmet need” in this area.

Curbing AMR through sustainable antibiotic manufacturing