Cubist Reports Positive Results From Phase 3 Trial Of Ceftolozane/Tazobactam

(RTTNews) - Cubist Pharmaceuticals Inc. (CBST) announced positive top-line results from its pivotal Phase 3 clinical trial of its antibiotic candidate ceftolozane/tazobactam in complicated intra-abdominal infections or cIAI.

The company noted that Ceftolozane/tazobactam, in combination with metronidazole, met the U.S. Food and Drug Administration or FDA and the European Medicines Agency or EMA defined primary endpoints of statistical non-inferiority compared to meropenem. The primary endpoint was a clinical cure rate 26 - 30 days after the initiation of therapy (the Test of Cure visit).

For the FDA, the primary analysis was conducted in the Microbiological Intent-to-Treat (MITT) population; the non-inferiority margin was 10%; and the lower and upper bounds of the 95% confidence interval were -8.9% and 0.5%, respectively.

For the EMA, the primary analysis population was Clinically Evaluable or CE patients; the non-inferiority margin was 12.5%; and the lower and upper bounds of the 99% confidence interval were -4.2% and 4.3%, respectively. Results of the secondary analysis were consistent with and supportive of the primary outcome.

The treatment emergent adverse event rate for ceftolozane/tazobactam, in combination with metronidazole, was 44.0% and for meropenem was 42.7%. In this trial, the most commonly reported adverse events for ceftolozane/tazobactam in combination with metronidazole were nausea (7.9%), diarrhea (6.2%), fever (5.2%), insomnia (3.5%), and vomiting (3.3%). This adverse event profile is consistent with that seen with other cephalosporin antibiotics and comparable to meropenem in this trial.

In the cIAI trial, the spectrum of pathogens seen was typical with that seen in other pivotal trials in patients with these types of complicated infections. The most common Gram-negative pathogens observed in this trial included Escherichia coli(E. coli),Klebsiella pneumoniae (K. pneumoniae) and Pseudomonas aeruginosa (P. aeruginosa).

The company stated that the cIAI trial results followed the positive data reported last month from a Phase 3 trial of ceftolozane/tazobactam compared to levofloxacin in patients with complicated urinary tract infections or cUTI.

Based on the success of the cUTI and cIAI trials, Cubist said it expects to submit a New Drug Application or NDA to the FDA in the first half of 2014 for approval in both of these indications. In the second half of 2014, the Company plans to submit a Marketing Authorization Application or MAA to the EMA.

Additionally, ceftolozane/tazobactam is being developed for the potential treatment of Hospital-Acquired Bacterial Pneumonia (HABP)/Ventilator-Associated Bacterial Pneumonia (VABP). The company noted that it expects to initiate a pivotal Phase 3 trial to assess the safety and efficacy of ceftolozane/tazobactam in this indication during the first half of 2014.