Roche antibiotic tackles serious drug-resistant pathogen
A scanning electron micrograph of a cluster of Acinetobacter baumanii bacteria
Scientists at Roche and Harvard University have discovered an entirely new class of antibiotic that can kill a highly drug-resistant ‘superbug’ with a mortality rate that can be upwards of 50% when the infection has spread into the blood.
The drug – called zosurabalpin – has been shown to be effective against carbapenem-resistant Acinetobacter baumannii or CRAB in animal models of serious infections and has now advanced into human testing, with first results due later this year.
CRAB ranks alongside antimicrobial-resistant (AMR) forms of Pseudomonas aeruginosa and Enterobacteriaceae on the World Health Organization’s list of the three pathogens that are most threatening to public health. All three are Gram-negative bacteria, which have an outer membrane containing lipopolysaccharide (LPS) molecules that can help protect them against antibiotics by blocking their uptake into cells.
If it proves effective in clinical trials, zosurabalpin could become the first new class of drug to treat Gram-negative bacterial infections in around 50 years. The macrocyclic peptide directly targets LPS, preventing the substance from being transported into the outer membrane of the bacterium, according to a pair of papers published in the journal Nature.
They describe how the drug – which inhibits a bacterial protein complex called LptB2FGC – was able to reduce levels of the pathogen in animals with CRAB-induced pneumonia and also reduce the death rate in animals with CRAB sepsis. Its discovery was remarkable, as thousands of other macrocyclic peptides showed little activity against the microbe.
If shown to be effective, the new drug could be a genuine lifeline for patients who currently have no treatment options, including carbapenems, which are often a last resort for AMR infections. CRAB kills hundreds of people in the US alone every year, according to Centers for Disease Control and Prevention (CDC) figures, although its incidence has been falling thanks to preventive measures.
Roche has completed phase 1 safety studies for zosurabalpin and will now move on to see if it can be effective against CRAB infections.
The emergence of a new antibiotic class is a major event in the fight against AMR, but even if it makes it through development and regulatory approval securing access by patients could be a challenge.
The main problem is that investment in developing new antimicrobials isn’t attractive, because when new drugs are developed they are used sparingly, reserved for patients with multidrug-resistant infections, so developers can’t get a return on their investment in R&D.
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, a bit like a Netflix or Amazon Prime account. The US and EU have been considering similar moves, but so far progress has been limited.
