Date: 2012-11-22
Type of information:
phase: 1
Announcement: initiation of a new study
Company: Basilea Pharmaceutica (Switzerland)
Product: BAL30072 (sulfactam antibiotic)
Action mechanism: BAL30072 is a novel sulfactam antibiotic that in in vitro and in vivo models demonstrated potent bactericidal activity against a broad range of multidrug-resistant Gram-negative pathogens such as Pseudomonas or Acinetobacter species. It overcomes bacterial resistance by several mechanisms and is not easily destroyed by bacterial beta-lactamase enzymes, such as extended-spectrum beta-lactamases (ESBLs), carbapenemases and the recently characterized New Delhi metallo-beta-lactamase 1 (NDM-1), which cause resistance against many currently marketed antibiotics.
Disease: multidrug-resistant Gram-negative infections
Therapeutic area: Infectious diseases
Country:
Trial
details:
Latest
news: * On November 22, 2012, Basilea Pharmaceutica has initiated the next planned pharmacokinetic phase 1 healthy volunteer study in its clinical development program for BAL30072. Another phase 1 study has been completed last year (see below).
* On October 25, 2011, Basilea has announced that it has completed the double-blind, randomized, placebo-controlled dose-ranging study in healthy volunteers assessing the pharmacokinetics, safety and tolerability of BAL30072 after multiple ascending doses of intravenous infusions. The drug was clinically well tolerated with no significant clinical adverse events. The limiting factor for the highest dose regimen tested was transiently elevated liver enzyme levels. The multiple ascending dose study was initiated following the successful completion of the single ascending dose phase I trial, in which BAL30072 was well tolerated and displayed dose-proportional pharmacokinetic properties. Following the analyses of the pharmacokinetic data obtained in the multiple-ascending dose study and the completion of ongoing preclinical studies such as PK/PD modeling in animals, Basilea plans to expand the phase I program in 2012 to include studies evaluating additional dosing regimens of BAL30072 mono and combination therapies in preparation to entering phase II studies of BAL30072 in patients with Gram-negative infections in 2013.
* On September 7, 2011, Basilea Pharmaceutica has announced the initiation of the second phase I study with its novel sulfactam antibiotic BAL30072. Following the successful completion of the single ascending dose phase I trial, in which BAL30072 was safe and well tolerated and displayed dose-proportional pharmacokinetic properties, Basilea is now commencing a double-blind, randomized, placebo-controlled study that assesses the pharmacokinetics, safety and tolerability of BAL30072 after multiple ascending intravenous infusions in healthy volunteers.
* On May 25, 2011, Basilea Pharmaceutica has reported positive top-line results from the first clinical phase I study with its antibiotic BAL30072 which is being developed for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. BAL30072 was safe and well tolerated in this single-ascending-dose study. The double-blind randomized clinical phase I study investigated the safety, tolerability and pharmacokinetics of single ascending doses of BAL30072 in healthy volunteers. BAL30072 was safe and well tolerated at all dose levels. It displayed dose-proportional plasma levels as well as linear pharmacokinetic properties. Detailed study results will be presented at upcoming scientific conferences. A clinical phase I multiple-ascending-dose study with BAL30072 is anticipated to start in the second half of 2011.
* On May 9, 2011, new research data on Basilea's antibacterial compounds was presented in Milan, Italy, at the European Congress of Clinical Microbiology and Infectious Disease (ECCMID) and the International Congress of Chemotherapy (ICC) joint meeting. Basilea's novel antibiotic BAL30072 was shown to be active against multidrug-resistant Gram-negative bacteria that express the NDM-1 resistance factor. Recently, Gram-negative bacteria that harbour the so-called New Delhi metallo-beta-lactamase 1 (NDM-1) alongside with several other resistance mechanisms have triggered increased medical concern. NDM-1 is an enzyme that leads to resistance towards antibiotics that have been the mainstay of treatment of clinically important pathogens such as Escherichia coli or Klebsiella pneumoniae. These bacteria may cause systemic infections including severe lung and complicated urinary tract infections. BAL30072 is resistant to degradation by NDM-1 and was therefore active, at clinically achievable concentrations, against many of the highly resistant isolates tested while standard anti-Gram-negative antibiotics such as meropenem, ceftazidime or aztreonam covered only a minority of the strains. BAL30072 and meropenem combined had enhanced activity and resulted in inhibition of more than 90% of the isolates.
Also at ECCMID/ICC, in-vitro data was presented that demonstrated the potent activity of BAL30072 against meropenem-resistant strains of Acinetobacter baumannii, a clinically important Gram-negative pathogen in hospital-acquired pneumonia, for which only few therapeutic options exist. BAL30072 was tested alongside reference drugs currently used for the treatment of Acinetobacter infections and showed greater activity than all the marketed beta-lactam antibiotics as well as most of the other comparators.
The new data confirm the therapeutic potential of Basilea's phase I compound BAL30072. The drug shows potent activity against a broad range of multidrug-resistant Gram-negative bacteria, including those harbouring NDM-1, and may offer a future treatment option for potentially life-threatening Gram-negative infections where currently only limited therapeutic options exist.
