New Antibiotic Enters Phase III Trials to Fight Superburg

Roche’s novel antibiotic zosurabalpin is  entering Phase III testing to determine its effectiveness in protecting against carbapenem-resistant Acinetobacter baumannii (CRAB), am antimicrobial resistance (AMR) drug, or “superbug,” that is considered an “urgent threat” by the Centers for Disease Control and Prevention (CDC). Roche began human testing of zosurabalpin 18 months earlier in hopes of it becoming the first new treatment for Gram-negative bacterial infections in around 50 years if it makes it through to regulatory approval.

The Phase III trial is scheduled to start toward the end of this year or early in 2026. In the trial, which will enroll approximately 400 patients around the world who are hospitalized with invasive CRAB infections and who are at risk of dying from the infection, zosurabalpi will be compared to standard-of-care treatment for CRAB infections, which kill hundreds of people in the U.S. every year, according to CDC data. Roche previously completed various Phase I studies that backed the drug’s safety, tolerability and pharmacokinetics, according to Roche.

Zosurabalpin, which was developed in collaboration with researchers at Harvard University, is a tethered macrocyclic peptide designed to interfere with the process in which Gram-negative bacteria build their outer lipopolysaccharide (LPS) membrane, which helps to protect them from being attacked by antimicrobial drugs. Zosurabalpin inhibits the trafficking of LPS from the interior of the bacteria into the outer membrane, a process that causes the bacteria to die.

According to Roche, zosurabalpin will not be affected by pre-existing resistance mechanisms, and its discovery could lay the foundations for future efforts to tackle AMR, which, by some estimates, could cause up to 10 million deaths annually by 2050, equaling current fatalities from cancer. “Zosurabalpin is a so-called ‘narrow spectrum’ antibiotic, meaning that it has activity against Acinetobacter specifically,” said Roche’s head of immunology product development Larry Tsai, MD. “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.”

The World Health Organization says CRAB is one of the highest priority pathogens among those most threatening to public health. “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,” added Dr. Tsai