Investigational Antibiotic Meets Primary Endpoint in Second of Two Indications
LEXINGTON, MA, USA I December 16, 2013 I 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 intra-abdominal infections (cIAI). Ceftolozane/tazobactam, in combination with metronidazole, met the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (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 (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 cIAI trial results follow the positive data reported last month from a Phase 3 trial of ceftolozane/tazobactam compared to levofloxacin in patients with complicated urinary tract infections (cUTI).
“This is a significant and exciting milestone in our quest to provide new antibiotics to treat patients with serious and often life-threatening infections caused by drug-resistant bacteria,” said Steven Gilman, Ph.D., Executive Vice President of Research and Development and Chief Scientific Officer of Cubist Pharmaceuticals. “With positive results from Phase 3 clinical trials of ceftolozane/tazobactam in both cUTI and cIAI, we look forward to submitting these data to global regulatory authorities and presenting the full results at upcoming medical meetings.”
According to Philip S. Barie, M.D., M.B.A., Professor of Surgery and Public Health at Weill Cornell Medical College, attending surgeon at New York-Presbyterian Hospital/Weill Cornell Medical Center, and Executive Director of the Surgical Infection Society Foundation for Research and Education, “These data are encouraging as we face alarmingly increasing rates of bacterial resistance. There is an urgent need for new antibiotics, especially in the hospital setting, in order to be able to manage effectively those conditions complicated by serious infections, including those caused by resistant Gram-negative bacteria.”
Based on the success of the cUTI and cIAI trials, Cubist expects to submit a New Drug Application (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 (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 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.
About the Ceftolozane/tazobactam Phase 3 cIAI Trial
Results from the pivotal Phase 3 cIAI 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) plus metronidazole (0.5 g q8h), to meropenem, administered intravenously (1 g q8h), in adult patients (total n=993) with cIAI. 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 and metronidazole to the comparator meropenem with respect to the proportion of patients in the Microbiological Intent-to-Treat (MITT) population who achieve clinical cure at the Test of Cure (TOC) visit 26 – 30 days after the first dose of the study drug is administered. The primary endpoint of the trial for the EMA was to establish non-inferiority of ceftolozane/tazobactam and metronidazole to the comparator meropenem with respect to the proportion of patients in the Clinically Evaluable (CE) population.
Dr. Barie is a consultant to Cubist, serving on the Advisory Board of the ceftolozane/tazobactam program.
About Ceftolozane/tazobactam
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 β-lactamase inhibitor. The addition of tazobactam broadens coverage to include most Extended-spectrum β-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) and Complicated Intra-Abdominal Infections (cIAI). In pivotal Phase 3 clinical trials of ceftolozane/tazobactam in cUTI when studied against levofloxacin and of ceftolozane/tazobactam, in combination with metronidazole, in cIAI when studied against meropenen, ceftolozane/tazobactam met its primary endpoints of statistical non-inferiority. Ceftolozane/tazobactam is also being developed for the potential treatment of Hospital-Acquired Bacterial Pneumonia (HABP)/Ventilator-Associated Bacterial Pneumonia (VABP) at a dose of 3 g every 8 hours. 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 β-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 mechanisms 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.
About Cubist
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.
SOURCE: Cubist Pharmaceuticals
Post Views: 43
Investigational Antibiotic Meets Primary Endpoint in Second of Two Indications
LEXINGTON, MA, USA I December 16, 2013 I 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 intra-abdominal infections (cIAI). Ceftolozane/tazobactam, in combination with metronidazole, met the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (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 (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 cIAI trial results follow the positive data reported last month from a Phase 3 trial of ceftolozane/tazobactam compared to levofloxacin in patients with complicated urinary tract infections (cUTI).
“This is a significant and exciting milestone in our quest to provide new antibiotics to treat patients with serious and often life-threatening infections caused by drug-resistant bacteria,” said Steven Gilman, Ph.D., Executive Vice President of Research and Development and Chief Scientific Officer of Cubist Pharmaceuticals. “With positive results from Phase 3 clinical trials of ceftolozane/tazobactam in both cUTI and cIAI, we look forward to submitting these data to global regulatory authorities and presenting the full results at upcoming medical meetings.”
According to Philip S. Barie, M.D., M.B.A., Professor of Surgery and Public Health at Weill Cornell Medical College, attending surgeon at New York-Presbyterian Hospital/Weill Cornell Medical Center, and Executive Director of the Surgical Infection Society Foundation for Research and Education, “These data are encouraging as we face alarmingly increasing rates of bacterial resistance. There is an urgent need for new antibiotics, especially in the hospital setting, in order to be able to manage effectively those conditions complicated by serious infections, including those caused by resistant Gram-negative bacteria.”
Based on the success of the cUTI and cIAI trials, Cubist expects to submit a New Drug Application (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 (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 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.
About the Ceftolozane/tazobactam Phase 3 cIAI Trial
Results from the pivotal Phase 3 cIAI 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) plus metronidazole (0.5 g q8h), to meropenem, administered intravenously (1 g q8h), in adult patients (total n=993) with cIAI. 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 and metronidazole to the comparator meropenem with respect to the proportion of patients in the Microbiological Intent-to-Treat (MITT) population who achieve clinical cure at the Test of Cure (TOC) visit 26 – 30 days after the first dose of the study drug is administered. The primary endpoint of the trial for the EMA was to establish non-inferiority of ceftolozane/tazobactam and metronidazole to the comparator meropenem with respect to the proportion of patients in the Clinically Evaluable (CE) population.
Dr. Barie is a consultant to Cubist, serving on the Advisory Board of the ceftolozane/tazobactam program.
About Ceftolozane/tazobactam
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 β-lactamase inhibitor. The addition of tazobactam broadens coverage to include most Extended-spectrum β-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) and Complicated Intra-Abdominal Infections (cIAI). In pivotal Phase 3 clinical trials of ceftolozane/tazobactam in cUTI when studied against levofloxacin and of ceftolozane/tazobactam, in combination with metronidazole, in cIAI when studied against meropenen, ceftolozane/tazobactam met its primary endpoints of statistical non-inferiority. Ceftolozane/tazobactam is also being developed for the potential treatment of Hospital-Acquired Bacterial Pneumonia (HABP)/Ventilator-Associated Bacterial Pneumonia (VABP) at a dose of 3 g every 8 hours. 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 β-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 mechanisms 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.
About Cubist
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.
SOURCE: Cubist Pharmaceuticals
Post Views: 43
