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."

TAXIS Pharmaceuticals announced yesterday that it has received a 3-year, $2.9 million grant from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) to develop a novel treatment for multidrug-resistant (MDR) gonorrhea.

TAXIS will use the money to advance research and development efforts into dihydrofolate reductase inhibitors (DHFRIs), which target and inhibit an essential bacterial enzyme that plays a role in DNA, RNA, and protein synthesis. Experiments conducted in animals have demonstrated the ability of DFHRIs to successfully eradicate MDR gonorrhea.

With an estimated 82 million new cases annually, gonorrhea is one of the world's most common sexually transmitted infections, and is steadily developing resistance to the last line of effective antibiotic treatment—ceftriaxone. Left untreated, gonorrhea can cause a host of serious health issues, including pelvic inflammatory disease and infertility.

"Our DHFRIs have demonstrated pre-clinical potential in overcoming resistance barriers, offering a significant breakthrough for future treatment," TAXIS Principal Investigator and Chief Scientific Officer Ajit Parhi, PhD, said in a company press release. "This NIH grant further validates our scientific approach and the vital role that DHFRIs can play in addressing this growing public health challenge."

CARB-X provides new funds for novel gonorrhea antibiotic

In related news, Swiss biopharmaceutical company Debiopharm said today that it has received additional funding from CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) to continue development of Debio1453, a first-in-class antibiotic candidate with a novel mechanism of action against Neisseria gonorrhoeae.

Debiopharm initially received funding from CARB-X in 2017 for pre-clinical development of Debio1453, which inhibits an essential fatty acid synthesis enzyme found in N gonorrhoeae and other bacteria. The company says the newly awarded grant, projected to amount to $12.3 million, will help advance the project to first-in-human evaluation.

"This further confirms our strong pre-clinical proof-of-concept obtained for the treatment of gonorrhea," Morgane Vanbiervliet, Debiopharm's director of global development and licensing, said in a company press release. "CARB-X's commitment closely aligns with our own vision to establish a new standard of care for the treatment of N. gonorrhoeae infections, by developing an antibiotic with an entirely new mechanism of action and offering a crucial treatment alternative against multi-drug-resistant infections."

Cambodia's ministry of health has reported its fourth fatal human H5N1 avian flu case of the year, which involves an 11-year-old boy from Kampong Speu province in the south central part of the country, according to an official Facebook statement translated and posted by Avian Flu Diary, an infectious disease news blog.

The boy died yesterday after he arrived at a hospital with severe symptoms. On the same day, tests at the Pasteur Institute in Cambodia confirmed that his samples were positive for H5N1.

An investigation revealed reports of illnesses and deaths in chickens and ducks near the boy's home about a week before his symptoms began. 

Continued rise of cases in Cambodia

Cambodia reported its last H5N1 case in March, which involved a 3-year-old boy from Kratie province who also died.

The country has reported a rise in H5N1 infections since the end of 2023. Some have been linked to a novel reassortment between an older 2.3.2.1c clade known to circulate in Southeast Asia's poultry and genes from the newer 2.3.4.4b clade that's spreading globally. So far, it's not known what clade infected the 11-year-old boy.