Lexington, Mass., November 25, 2013 – Cubist Pharmaceuticals, Inc. (NASDAQ: CBST) today announced positive top-line results from the Company’s pivotal Phase 3 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% non-inferiority margin). The primary endpoint is a composite of microbiological eradication and clinical cure rate (composite cure rate) at 5 - 9 days after end of therapy (the Test of Cure visit). The 95% confidence interval around the treatment difference had lower and upper bounds of 2.3% and 14.6%, 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% confidence interval around the positive treatment differences in favor 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 complicated urinary tract infections.
The treatment emergent adverse event rate for ceftolozane/tazobactam was 34.7% and for levofloxacin was 34.4%. In this trial, the most commonly reported adverse events for ceftolozane/tazobactam were headache (5.8%), constipation (3.9%), hypertension (3%), nausea (2.8%), and diarrhea (1.9%). This adverse event profile is consistent with that seen with ceftolozane/tazobactam in the prior Phase 2 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 3 trial in complicated intra-abdominal infections.”
Cubist is concluding a pivotal Phase 3 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.
Additionally, ceftolozane/tazobactam is being developed for the potential treatment of Hospital-Acquired Bacterial Pneumonia (HABP)/Ventilator-Associated Bacterial Pneumonia (VABP). The Company expects to initiate a pivotal Phase 3 trial to assess the safety and efficacy of ceftolozane/tazobactam (at a dose of 3 g every 8 hours) in this indication during the first half of 2014.
About the Ceftolozane/tazobactam Phase 3 cUTI Trial
Results from the pivotal Phase 3 cUTI clinical trial include data from two multi-center, 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 U.S. 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.
Ceftolozane/tazobactam, an antibiotic candidate being developed to treat certain Gram-negative infections, consists of ceftolozane, a novel cephalosporin that has demonstrated more potent in vitro activity against Pseudomonas aeruginosa as compared to the currently available cephalosporins, with tazobactam, a well-established ?-lactamase inhibitor. The addition of tazobactam broadens coverage to include most Extended-spectrum ?-lactamase (ESBL)-producing Escherichia coli (E. coli), Klebsiella pneumoniae, and other Enterobacteriaceae. Ceftolozane/tazobactam is being developed for the potential treatment of Complicated Urinary Tract Infections (cUTI), Complicated Intra-Abdominal Infections (cIAI), and Hospital-Acquired Bacterial Pneumonia (HABP)/Ventilator-Associated Bacterial Pneumonia (VABP).
Ceftolozane/tazobactam has been granted Fast Track status, pursuant to the GAIN Act, by the U.S. Food and Drug Administration (FDA) for its respective Qualified Infectious Disease Product (QIDP) indications. The QIDP designation for ceftolozane/tazobactam allows for certain incentives related to the development of new antibiotics, including eligibility for Fast Track status and Priority Review.
About Gram-negative Bacteria
There has been a worldwide increase in the number of infections caused by Gram-negative bacteria. Highly adaptive pathogens that can develop resistance through several mechanisms, resistant Gram-negative bacteria are a serious global public health concern. Collectively, Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae) and Pseudomonas aeruginosa (P. aeruginosa) account for 27% of all pathogens and 70% of all Gram-negative pathogens causing healthcare-associated infections (HAIs). Gram-negative bacteria are common causes of intra-abdominal infections (IAIs), urinary tract infections (UTIs), and nosocomial, or hospital-acquired, pneumonia, as well as bacteremia (bloodstream infections). E. coli is the most common cause of UTIs, and cases of UTI caused by Extended-spectrum ?-lactamase (ESBL)-producing E. coli and K. pneumoniae, as well as P. aeruginosa, including drug-resistant strains, are increasing. ESBL-producing E. coli and K. pneumoniae are also frequently isolated in patients with complicated IAIs (cIAIs). Additionally, P. aeruginosa is the most common Gram-negative organism causing ventilator associated pneumonia and the second most common cause of catheter-associated UTIs. For more information reference a video on Gram-negative bacteria mechanism of resistance.
About Cubist’s Commitment to Antibiotic R&D
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 $300M USD in 2013 on antibacterial R&D and approximately 75% of its employee base is focused on the research, development, commercialization and support of antibiotics.
Cubist Pharmaceuticals, Inc. is a global biopharmaceutical company focused on the research, development, and commercialization of pharmaceutical products that address significant unmet medical needs in the acute care environment. Cubist is headquartered in Lexington, Massachusetts, with a central international office located in Zurich, Switzerland. Additional information can be found at Cubist’s web site at www.cubist.com.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Any statements contained herein which do not describe historical facts, including but not limited to, statements regarding: the top-line data and results from Cubist’s Phase 3 clinical trial studying ceftolozane/tazobactam in cUTI and the potential submission package to regulatory authorities requesting approval for ceftolozane/tazobactam in both of the cUTI and cIAI indications; the therapeutic potential of ceftolozane/tazobactam; the anticipated favorable impact resulting from the FDA designating ceftolozane/tazobactam as a QIDP, including eligibility for Fast Track status and Priority Review; the expected timing for announcing top-line data from our Phase 3 clinical trial studying ceftolozane/tazobactam in cIAI and for beginning trials studying the use of ceftolozane/tazobactam in HABP/VABP; our aspirations to achieve a portion of the IDSA’s goal of 10 new antibiotics by 2020; and the level of our financial and personnel commitments towards antibiotic research, development and commercialization, are forward-looking statements which involve risks and uncertainties that could cause actual results to differ materially from those discussed in such forward-looking statements. Such risks and uncertainties include, among others: regulatory developments in the United States and foreign countries; the outcome of final analyses of the data from Cubist’s recently-completed Phase 3 clinical trial of ceftolozane/tazobactam in cUTI may vary from our initial analysis, lead to different (including less favorable) interpretations of the results than the analyses conducted to date, identify important implications of the study that are not reflected in these statements, and the FDA and foreign regulatory authorities may not agree with our interpretation of such results; additional ongoing or planned clinical trials of ceftolozane/tazobactam, including our Phase 3 trial of ceftolozane/tazobactam in cIAI, may produce negative or inconclusive results; we may decide, or the FDA and foreign regulatory authorities may require us, to conduct additional clinical trials or to modify our ongoing clinical trials; we may experience delays in the commencement, enrollment, completion or analysis of clinical testing for ceftolozane/tazobactam, or significant issues regarding the adequacy of our clinical trial designs or the execution of our clinical trials, which could result in increased costs and delays, or limit our ability to obtain regulatory approval; the third parties upon whom we rely to conduct our clinical trials may not perform as expected; ceftolozane/tazobactam may not receive regulatory approval or be successfully commercialized, including as a result of regulatory authorities’ decisions regarding labeling and other matters that could affect its availability or commercial potential; unexpected adverse side effects or inadequate therapeutic efficacy of ceftolozane/tazobactam could delay or prevent regulatory approval or commercialization; our ability to maintain and enforce intellectual property protection for ceftolozane/tazobactam; competitive risks from current and future therapeutic alternatives to ceftolozane/tazobactam; HABP/VABP clinical trials of ceftolozane/tazobactam may not be successful or initiated or conducted in a timely manner; technical difficulties or excessive costs relating to the manufacture or supply of ceftolozane/tazobactam, including our ability to work with our third party contract manufacturers that manufacture and supply ceftolozane/tazobactam on our behalf; we may encounter other unanticipated or unexpected risks with respect to the development or manufacture of ceftolozane/tazobactam; the fact that drug discovery and development is complex, time consuming, expensive and fraught with a high risk of failure; and those additional factors discussed in our most recent annual report on Form 10-K and quarterly report on Form 10-Q filed with the Securities and Exchange Commission. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. These forward-looking statements speak only as of the date of this document, and we undertake no obligation to update or revise any of these statements.
Eileen C. McIntyre
Vice President, Investor Relations
Cubist Pharmaceuticals, Inc.
Director of Product Communications
Cubist Pharmaceuticals, Inc.
Deputy Managing Director, Health
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