Cubist acquired rights to develop and commercialize CXA-201 worldwide except in select Asia-Pacific and Middle East territories through Cubist's purchase of Calixa Therapeutics Inc. in December 2009. CXA-201 is the combination of a novel cephalosporin (CXA-101) with the beta-lactamase inhibitor tazobactam. Cubist is developing CXA-201 as a first-line intravenous therapy for the treatment of serious Gram-negative bacterial infections in the hospital, including those caused by multi-drug resistant Pseudomonas aeruginosa. CXA-201 has demonstrated potency against P. aeruginosa in in vitro studies, and the company believes that this is predictive of a highly differentiated profile versus marketed antibiotics.
Atlas of Infectious Diseases: Intra-Abdominal Infections, Hepatitis, and Gastroenteritis (Atlas of Infectious Diseases, Vol 7)
Cubist's Chief Medical Officer, Santosh Vetticaden, PhD, MD, said, "This clinical milestone represents an important advance in the development of CXA-201 and for our pipeline as we continue to build a portfolio of potential new therapies for acutely ill patients."
Steve Gilman, PhD, Cubist's Chief Scientific Officer said, "Multi-drug resistant Gram-negative infections represent a very important unmet medical need. CXA-201 has broad spectrum activity against Gram-negative pathogens, including multi-drug resistant Pseudomonas aeruginosa as well as most strains of ESBL-producing Enterobacteriaceae, which are serious pathogens for which limited therapeutic alternatives exist."
About Gram-negative bacteria
Gram-negative bacteria, such as P. aeruginosa, differ from Gram-positive bacteria, such as Staphylococcus aureus, in their cell wall structure. Gram-negative bacteria have an additional outer wall composed of phospholipids and lipopolysaccharides. This wall provides these bacteria an additional layer of defense for antibiotics to traverse. The outer wall contains efflux pumps that allow the bacteria to pump out substances toxic to the cell. Although Gram-positive bacteria also have these pumps, the Gram-negative strains are much more proficient, believed to be from an adaptation for living in watery environments. Examples of Gram-negative bacteria include Escherichia coli, P. aeruginosa, Klebsiella, and Acinetobacter. The diseases caused by Gram-negative bacteria include peritonitis, septicemia, pneumonia, neonatal meningitis, urinary tract infections, IAI, and burn and wound infections.
About Pseudomonas aeruginosa
Recent medical literature identifies P. aeruginosa as one of the most prevalent Gram-negative pathogens responsible for hospital-acquired infections, and points to its significant virulence and steeply increasing incidences in intensive care units (ICU). Data from the National Nosocomial Infections Surveillance of ICUs in the United States identified P. aeruginosa as the most frequently isolated Gram-negative strain, with an incidence almost doubling between 1975 and 2003. For example, an increase of P. aeruginosa from 9.6% to 16.3% was shown in nosocomial pneumonia and from 9.3% to 16.3% in urinary tract infections. Similar increases in P. aeruginosa-related infections were shown by the SENTRY Antimicrobial Surveillance Program for Europe, comparing data between 1997 and 2002. Pseudomonal infections can involve any part of the human body, but among the most common are urinary tract, lung, bloodstream, wound/burn, and intra-abdominal infections. Resistance to current treatment regimens for such infections is growing, with the increasing appearance of P. aeruginosa strains expressing multi-drug resistance against the commonly used first-line anti-pseudomonal antibiotics.
Source: Cubist Pharmaceuticals, Inc.
