Cubist Pharmaceuticals, Inc. announced the initiation of a pivotal phase III trial of CXA-201 in patients with complicated Urinary Tract Infections (cUTI). CXA-201 is being developed 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.

This trial is the first of two planned multi-centre, global, double-blind, randomized phase III studies to compare the safety and efficacy of CXA-201 relative to the comparator, levofloxacin, in patients with cUTI. The primary objective of the study is to establish non-inferiority of CXA-201 to the comparator with respect to the proportion of patients in the modified Microbiological Intent To Treat (mMITT) population who achieve both microbiological eradication and clinical cure at the test-of-cure (TOC) visit 5-9 days after the last dose of the study drug is administered. Cubist expects to enroll approximately 775 patients in this trial, which will also assess the safety of CXA-201 and investigate other pre-specified secondary endpoints.

Later this year, the company plans on initiating another pivotal global phase III trial of CXA-201 in patients with complicated Intra-Abdominal Infections (cIAI).

Brad Spellberg, MD, Associate Professor of Medicine at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Centre said, “The start of the phase III trial for CXA-201 is an important milestone for the infectious diseases community. CXA-201 is ‘the tip of the spear’ among several potential future treatments for resistant Gram negative infections that are in development in industry. CXA-201 is the first of them to enter phase III trials.”

Cubist’s chief medical officer Santosh Vetticaden, PhD, MD, said, “The start of this pivotal phase III trial represents a major milestone in the development of CXA-201, and we are extremely pleased to be making such a significant advance in this program that offers promise for the treatment of certain Gram-negative infections.”

The diseases caused by Gram-negative bacteria include peritonitis, septicemia, pneumonia, neonatal meningitis, urinary tract infections, intra-abdominal infections, and burn and wound infections. In the US in 2003, Gram-negative bacteria were associated with many of the most frequent types of hospital-acquired infections including 71% of urinary tract infections, 65% of pneumonia episodes, 34% of surgical site infections, and 24% of bloodstream infections. Important Gram-negative bacteria include Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii.

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 (ICUs). 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 percent to 16.3 percent was shown in nosocomial pneumonia and from 9.3 percent to 16.3 percent in urinary tract infections.

Similar increases in P. aeruginosa-related infections were shown by the SENTRY Antimicrobial Surveillance Programme 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.

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