Roche takes new antibiotic into phase 3 for 'urgent threat'
Roche is moving its novel antibiotic zosurabalpin into phase 3 testing for carbapenem-resistant Acinetobacter baumannii (CRAB), a 'superbug' that is considered an 'urgent threat' by the CDC, in what could be a big step forward in the fight against antimicrobial resistance (AMR).
The move into pivotal testing comes less than 18 months after Roche started human testing of zosurabalpin, which could become the first new treatment for Gram-negative bacterial infections in around 50 years if it makes it through to regulatory approval.
Roche is targeting CRAB due to the desperate need for new antibiotics to treat the infection, which the WHO says is one of the highest priority pathogens among those most threatening to public health.
Its phase 3 trial, which is scheduled to start towards the end of this year or early in 2026, will enrol around 400 patients around the world who are hospitalised with invasive CRAB infections and who are at risk of dying from their infection.
The new antibiotic will be compared to standard-of-care treatment for CRAB infections, which kill hundreds of people in the US alone every year, according to CDC data. The decision to move into phase 3 testing follows the completion of various phase 1 studies that backed the drug's safety, tolerability, and pharmacokinetics, according to Roche.
The drug – developed in collaboration with researchers at Harvard University in the US – is a tethered macrocyclic peptide (MCP) that is 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, and blocking that process 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, equalling 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.
"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," he added.
"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."
Alongside zosurabalpin, the Swiss pharma group is also developing another new-mechanism antibiotic – LepB inhibitor RG6436 – which is in early-stage clinical development for carbapenem-resistant Gram-negative infections, initially focusing on complicated urinary tract infections (UTIs).
The emergence of a new antibiotic class is an important event in the fight against AMR, as drugmakers have been retreating from antimicrobial development in droves in recent decades, as it is hard to get a return on the investment made. That is because when new drugs are developed, they tend to be used sparingly, reserved for patients with multidrug-resistant infections.
Some governments have implemented incentives to try to adjust the health economics challenges. Notably, the UK has introduced a new subscription model that provides annual payments regardless of the amount of drug used.
