Cubist Pharmaceuticals, Inc, a leading acute care therapeutics company, has enrolled first patient in a phase-2 study with CXA-201. This multicenter, double-blind, randomized, study will compare the safety and efficacy of intravenous CXA-201 with an active comparator in patients with complicated intra-abdominal infections (cIAI). This international study is expected to enrol 120 patients.

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.

Cubist’s chief medical officer, Santosh Vetticaden, 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, 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.”

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.

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).

Cubist Pharma is a biopharmaceutical company focused on the research, development, and commercialization of pharmaceutical products that address unmet medical needs in the acute care environment.