
Swiss drugmaker Roche says it is planning to launch a phase 3 trial of its novel antibiotic candidate zosurabalpin in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections.
The safety and efficacy study will compare the outcomes of zosurabalpin versus standard-of-care antibiotics in an estimated 400 patients with CRAB infections at sites across Europe, North and South America, and Asia. Roche says the trial is expected to launch at the end of the year or in early 2026.
Zosurabalpin is a tethered macrocyclic peptide (MCP) antibiotic that was identified through the screening of nearly 45,000 compounds. As described in two papers published in Nature in January 2024 by scientists at Roche and Harvard University, MCPs work by blocking the transport of lipopolysaccharide from the inner bacterial membrane to the outer membrane, which is essential for outer membrane formation and antibiotic resistance in A baumannii.
Subsequent testing showed zosurabalpin was highly effective in lab tests against human clinical CRAB isolates and in mice with lung and thigh infections caused by pan–drug-resistant A baumannii. Roche says phase 1 clinical studies of safety, tolerability, and pharmacodynamics support further development of the drug, which is not affected by pre-existing resistance mechanisms.
Priority for antibiotic development
CRAB infections can be a serious and deadly threat for hospital patients. With mortality estimates for invasive infections ranging from 40% to 60% and limited treatment options, CRAB is considered one of the most dangerous antibiotic-resistant pathogens by the World Health Organization and the US Centers for Disease Control and Prevention and a priority for antibiotic development.
"Drug-resistant Acinetobacter are present in every country of the world and disproportionately impact patients who are in hospital, causing invasive infections like pneumonia and bloodstream infections/sepsis," Larry Tsai, MD, Roche's senior vice president and global head of immunology product development, said in a statement emailed to reporters. "Roche hopes that further clinical trials will demonstrate that zosurabalpin can help tackle the rising issue of antibiotic resistance and contribute to addressing a major infectious disease challenge to public health."