Cubist Pharmaceuticals, Inc., a global biopharmaceutical company, has reported positive top-line results from the its pivotal phase III clinical trial of its antibiotic candidate ceftolozane/tazobactam in complicated urinary tract infections (cUTI). Ceftolozane/tazobactam met its primary endpoint of statistical non-inferiority compared to levofloxacin (10 per cent non-inferiority margin).
The primary endpoint is a composite of microbiological eradication and clinical cure rate (composite cure rate) at five to nine days after end of therapy (the Test of Cure visit). The 95 per cent confidence interval around the treatment difference had lower and upper bounds of 2.3 per cent and 14.6 per cent, respectively, favoring ceftolozane/tazobactam. Results of the secondary analyses were consistent with and supportive of the primary outcome.
Although this trial was not prospectively designed to demonstrate superiority, the finding that the lower bound of the 95 per cent confidence interval around the positive treatment differences in favour of ceftolozane/ tazobactam was greater than zero indicated statistical superiority over levofloxacin in this trial.
The spectrum of Gram-negative pathogens seen in this trial was typical of that seen in other clinical trials in patients with cUTI.
The treatment emergent adverse event rate for ceftolozane/tazobactam was 34.7 per cent and for levofloxacin was 34.4 per cent. In this trial, the most commonly reported adverse events for ceftolozane/tazobactam were headache (5.8 per cent), constipation (3.9 per cent), hypertension (three per cent), nausea (2.8 per cent), and diarrhea (1.9 per cent). This adverse event profile is consistent with that seen with ceftolozane/tazobactam in the prior phase II trial in cUTI and comparable to levofloxacin in this trial.
“We are very pleased with these positive results, which represent a significant milestone for both ceftolozane/tazobactam and Cubist,” said Steven Gilman, Ph.D., executive vice president of Research and Development and chief scientific officer of Cubist Pharmaceuticals. “As the global leader in antibiotic research and development, Cubist is committed to combating the growing threat of resistant bacteria and providing needed therapies for patients with serious infections. We look forward to the upcoming data on ceftolozane/tazobactam from our phase III trial in complicated intra-abdominal infections.”
Cubist is concluding a pivotal phase III trial of ceftolozane/tazobactam in patients with complicated intra-abdominal infections (cIAI). This study in patients with cIAI is comparing the safety and efficacy of ceftolozane/ tazobactam in combination with metronidazole relative to the comparator meropenem. The Company expects to announce cIAI top-line data in late December and, as previously agreed to with regulatory authorities, the cUTI and cIAI data together will form the potential submission package to regulatory authorities requesting approval in both indications.
Results from the pivotal phase III cUTI clinical trial include data from two multi-centre, global, double-blind, randomized studies. The trial compared the safety and efficacy of ceftolozane/tazobactam, administered intravenously (1.5 g q8h), to levofloxacin, administered intravenously (750 mg qd), in adult patients (total n=1050) with cUTI, including those where the infection spread to the kidney (pyelonephritis). The primary endpoint of the trial, as defined in collaboration with the US Food and Drug Administration, was to establish non-inferiority of ceftolozane/tazobactam to the comparator levofloxacin 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. The primary endpoint in the European Union of non-inferiority based on microbiological eradication was also met.
Cubist has a growing commitment to global public health through its leadership in the R&D of antibiotics to treat serious and life-threatening infections caused by a broad range of increasingly resistant bacteria. The Company hopes to deliver at least four new antibiotics in support of the Infectious Diseases Society of America (IDSA) goal of 10 new antibiotics by 2020. Cubist is investing over US$ 300M in 2013 on antibacterial R&D and approximately 75 per cent of its employee base is focused on the research, development, commercialization and support of antibiotics.
Cubist Pharmaceuticals, Inc. is focused on the research, development, and commercialization of pharmaceutical products that address significant unmet medical needs in the acute care environment.