“Gram-negative bacteria” pose a huge threat to public health. With deathly adaptability, these types of bacteria are able to develop resistance to many antibiotics and survive in a wide range of conditions. In particular, Acinetobacter baumannii, also known as CRAB, is one of clinical medicine’s most antibiotic resistant pathogens, killing hundreds in the U.S. every year with estimated mortality rates ranging from 26.0% to 55.7%.
But a new antibiotic from Swiss pharmaceutical company Roche could change the future of how we treat Gram-negative bacteria. Roche announced on Monday that its antibiotic zosurabalpin will enter phase 3, late-stage human trials, by the end of this year or early next year.
If successful, the drug will be the first new class of antibiotics targeting Gram-negative bacteria to be developed in over 50 years.
What makes Gram-negative bacteria so hard to treat?
Antibiotics treat illness by killing bacteria or suspending bacterial growth. But in order to access and attack crucial parts of the bacteria, most antibiotics must first pass through their outer membranes.
However, Gram-negative bacteria are distinguished from other forms of bacteria because they are protected by a second outer membrane. These outer membranes are covered in protective molecules called lipopolysaccharides (LPS), which stabilize the membranes and create a barrier to most drugs and antibiotics.
This resistance makes Gram-negative bacteria extremely tricky to treat, especially with patients who are already immunocompromised. It causes around a fifth of ICU infections, and most cases of ventilator-associated pneumonia, bloodstream infections related to catheters, and sepsis developed from the ICU.
How does zosurabalpin help?
Roche collaborated with Harvard researchers to develop a new way to stop Gram-negative bacteria. They found that the key was to inhibit the transportation of LPS molecules, the armor that creates the structure of the bacteria’s outer membrane.
Zosurabalpin is able to destroy Gram-negative bacteria by jamming LPS molecules inside the bacteria, weakening its membrane. It is the first of its class of antibiotics, and the first new class of antibiotics for Gram-negative bacteria since 1968.
“This antibiotic is important, but it can also serve as a catalysis point for future innovation,” said Michael Lobritz, global head of infectious diseases at Roche, to the Financial Times. “There are very few [new classes of antibiotics] . . . that have been discovered in the last 15 years. So if you are able to launch a new one, we can build off that for decades to come.”
Basel-based Roche has a vast portfolio that includes treatments for cancer, severe eye diseases, and multiple sclerosis. The company reported sales of roughly $68.7 billion in 2024, marking growth of 7% over the previous year on a constant exchange rate basis.
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