BAL30072

BAL30072 is a novel sulfactam antibiotic with potent antimicrobial activity against a broad range of Gram-negative bacteria, including clinically increasingly problematic multidrug-resistant pathogens such as Pseudomonas aeruginosa, Acinetobacter spp., Klebsiella spp. and Enterobacter spp.

BAL30072 is stable towards many types of beta-lactamases that can deactivate most of the currently marketed beta-lactam antibiotics such as cephalosporins and carbapenems. The compound is taken up very readily into bacteria, exploiting essential nutrient uptake systems and is able to circumvent resistance caused by changes in the outer membrane of Gram-negative bacteria. In experimental settings, bacterial resistance towards BAL30072 develops more slowly than it does to other drugs.

The compound has shown to be highly compatible with agents used for treating Gram-positive infections and even works synergistically with some agents used for treating Gram-negative infections, such as carbapenems and aminoglycosides.

 

Due to its potent antimicrobial activity against a broad range of clinically relevant Gram-negative bacteria, BAL30072 has the potential to be used for patients with serious and life-threatening infections such as hospital-acquired pneumonia (including ventilator-associated pneumonia), complicated intra-abdominal infections or complicated urinary tract infections.

Ongoing phase I program

Basilea initiated the clinical phase I program in November 2010. Following the successful completion of a single ascending dose phase I trial, in which BAL30072 was safe and well tolerated and displayed dose-proportional pharmacokinetic properties, Basilea has started a double-blind, randomized, placebo-controlled study that assesses the pharmacokinetics, safety and tolerability of BAL30072 after multiple ascending intravenous infusions in healthy volunteers.

The need for new Gram-negative antibiotics

Antibiotic-resistance is a chronic problem for the infectious disease field. Many pathogens will eventually develop mechanisms that enable them to deactivate even the most potent antibiotics in the medical arsenal.

In hospitals, beta-lactam antibiotics form the main-stay antimicrobial therapy but their use is increasingly compromised by acquired beta-lactam resistance, especially in Gram-negative bacteria such as Enterobacteriaceae and Pseudomonas aeruginosa. In a recent survey involving thousands of patients from hospitals around the world, Gram-negative bacteria have been found in sixty percent of clinical isolates in intensive care units.

The need for novel Gram-negative antibiotics with a broad coverage of clinically relevant pathogens is therefore undeniable and will further emerge as there are currently no compounds in late-stage development in this space.