DUBLIN, June 20, 2016 /PRNewswire/ -- Allergan plc (NYSE: AGN), a leading global pharmaceutical company committed to developing new treatment options for infectious diseases, today presented new data highlighting the in vitro activity of AVYCAZ® (ceftazidime and avibactam) against several species of Gram-negative pathogens, including certain strains of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and Pseudomonas aeruginosa. Results were presented at the 2016 ASM Microbe meeting in Boston (June 16-20, 2016) in two separate studies—one of which featured data from the International Network for Optimal Resistance Monitoring (INFORM) program, one of the largest ongoing pathogen surveillance programs in the United States.
Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria are a type of carbapenen-resistant Enterobacteriaceae (CRE), which the Centers for Disease Control and Prevention (CDC) has identified as one of the three most urgent public health threats specific to antibiotic resistance. KPC accounts for approximately 85 percent of all CRE infections in the U.S. resistant Pseudomonas aeruginosa is also considered a serious threat by the CDC 1
"KPC and Pseudomonas aeruginosa represent two of the most serious pathogens causing healthcare-associated infections and are a major challenge in many of today's hospitals," said David Nicholson, Ph.D., President and Executive Vice President, Global R&D, Allergan. "These data and other learnings from the INFORM program reflect Allergan's continued commitment to research that advances our understanding of difficult-to-treat Gram-negative pathogens and guides our ongoing development of treatments for serious infections."
One of the studies found AVYCAZ inhibited the majority of isolates evaluated in vitro from 11 Enterobacteriaceae species, including E. coli and KPC-producing Gram-negative bacteria. This study, presented in a poster titled "Ceftazidime-avibactam (CAZ-AVI) activity tested against eleven Enterobacteriaceae (ENT) species producing KPC enzymes," included an evaluation of 662 KPC-producing Enterobacteriaceae clinical isolates collected worldwide from 2009 to 2014. Susceptibility testing was performed on each isolate for AVYCAZ, meropenem, amikacin, tigecycline and colistin using reference broth microdilution methods, and breakpoint criteria from the U.S. Food and Drug Administration (FDA) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) were applied to the test results.
A second and separate study, presented in a poster titled "Activity of Ceftazidime-Avibactam Tested Against Clinical Isolates of Antimicrobial Resistant Pseudomonas aeruginosa (PSA) from United States (USA) Medical Centers (2012-2014)," found AVYCAZ exhibited in vitro activity against the majority of evaluated Pseudomonas aeruginosa strains, and retained activity against resistant isolates. This study evaluated 5,643 Pseudomonas aeruginosa isolates collected from 2012 to 2014 from 74 U.S. medical centers in the INFORM Surveillance Program, part of a research effort developed and supported by Allergan that monitors the prevalence and changing trends of resistant bacteria, as well as the in vitro activity of antibiotics against these pathogens. Susceptibility testing was performed on each isolate for AVYCAZ, ceftazidime alone, meropenem, piperacillin-tazobactam and amikacin using reference broth microdilution methods, and breakpoint criteria from the U.S. FDA were applied to the test results.
AVYCAZ is an antibiotic developed to treat certain serious Gram-negative bacterial infections. It consists of ceftazidime, a third-generation cephalosporin that is an established and respected treatment for serious Gram-negative bacterial infections, and avibactam, a non-β lactam β-lactamase inhibitor.
The determination of efficacy of AVYCAZ was supported in part by the previous findings of the efficacy and safety of ceftazidime for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). The contribution of avibactam to AVYCAZ was primarily established in vitro and in animal models of infection. AVYCAZ was studied in two Phase 2 randomized, blinded, active-controlled, multicenter trials, one each in cIAI and cUTI. These trials were not designed with any formal hypotheses for inferential testing against the active comparators.
The addition of avibactam to ceftazidime protects ceftazidime from breakdown by certain β-lactamases. AVYCAZ offers a differentiated profile in the treatment of cIAI (in combination with metronidazole) and cUTI caused by designated microorganisms through its in vitro activity against Enterobacteriaceae, including those that produce certain extended-spectrum β-lactamases (ESBLs) and Klebsiella pneumoniae carbapenemase (KPC), and difficult-to-treat Pseudomonas aeruginosa.
Ceftazidime and avibactam is being jointly developed with AstraZeneca. Allergan holds the rights to commercialize ceftazidime and avibactam in North America, while AstraZeneca holds the rights to commercialize the combination in the rest of the world.
INDICATIONS AND USAGE
As only limited clinical safety and efficacy data for AVYCAZ (ceftazidime and avibactam) are currently available, reserve AVYCAZ for use in patients who have limited or no alternative treatment options.
Complicated Intra-Abdominal Infections (cIAI)
AVYCAZ, in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections (cIAI) caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia stuartii, Enterobacter cloacae, Klebsiella oxytoca and Pseudomonas aeruginosa in patients 18 years or older.
Complicated Urinary Tract Infections (cUTI), including Pyelonephritis
AVYCAZ is indicated for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii, Proteus spp., and Pseudomonas aeruginosa in patients 18 years or older.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of AVYCAZ and other antibacterial drugs, AVYCAZ should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.
IMPORTANT SAFETY INFORMATION
AVYCAZ is contraindicated in patients with known serious hypersensitivity to the components of AVYCAZ (ceftazidime and avibactam), avibactam‑containing products, or other members of the cephalosporin class.
WARNINGS AND PRECAUTIONS
- In a Phase 3 complicated intra-abdominal infections (cIAI) trial, clinical cure rates were lower in a subgroup of patients with baseline creatinine clearance (CrCL) of 30 to less than or equal to 50 mL/min compared to those with CrCL greater than 50 mL/min. The reduction in clinical cure rates was more marked in patients treated with AVYCAZ plus metronidazole compared to meropenem-treated patients. Clinical cure rates in patients with normal renal function/mild renal impairment (CrCL greater than 50 mL/min) was 85% (322/379) with AVYCAZ plus metronidazole vs 86% (321/373) with meropenem, and clinical cure rates in patients with moderate renal impairment (CrCL 30 to less than or equal to 50 mL/min) was 45% (14/31) with AVYCAZ plus metronidazole vs 74% (26/35) with meropenem. Within this subgroup, patients treated with AVYCAZ received a 33% lower daily dose than is currently recommended for patients with CrCL 30 to less than or equal to 50 mL/min. Monitor CrCL at least daily in patients with changing renal function and adjust the dosage of AVYCAZ accordingly.
- Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with AVYCAZ is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. Exercise caution if this product is to be given to a penicillin or other beta-lactam-allergic patient because cross sensitivity among beta-lactam antibacterial drugs has been established. Discontinue the drug if an allergic reaction to AVYCAZ occurs.
- Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs, including AVYCAZ, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial drugs. If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible.
- Seizures, nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported in patients treated with ceftazidime, particularly in the setting of renal impairment. Adjust dosing based on creatinine clearance.
- Prescribing AVYCAZ in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
- The most common adverse reactions (incidence of ≥10% in either indication) were vomiting (14%), nausea (10%), constipation (10%), and anxiety (10%).
Please see full Prescribing Information for AVYCAZ at www.avycaz.com.
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a unique, global pharmaceutical company and a leader in a new industry model—Growth Pharma. Allergan is focused on developing, manufacturing, and commercializing innovative branded pharmaceuticals, high-quality generic and over-the-counter medicines, and biologic products for patients around the world.
Allergan markets a portfolio of best-in-class products that provide valuable treatments for the central nervous system, eye care, medical aesthetics, gastroenterology, women's health, urology, cardiovascular and anti-infectives therapeutic categories, and operates the world's third-largest global generics business, providing patients around the globe with increased access to affordable, high-quality medicines. Allergan is an industry leader in research and development, with one of the broadest development pipelines in the pharmaceutical industry and a leading position in the submission of generic product applications globally.
With commercial operations in approximately 100 countries, Allergan is committed to working with physicians, health care providers, and patients to deliver innovative and meaningful treatments that help people around the world live longer, healthier lives.
For more information, visit Allergan's website at www.allergan.com.
Statements contained in this press release that refer to future events or other non-historical facts are forward-looking statements that reflect Allergan's current perspective of existing trends and information as of the date of this release. Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements. Actual results may differ materially from Allergan's current expectations depending upon a number of factors affecting Allergan's business. These factors include, among others, the difficulty of predicting the timing or outcome of FDA approvals or actions, if any; the impact of competitive products and pricing; market acceptance of and continued demand for Allergan's products; difficulties or delays in manufacturing; and other risks and uncertainties detailed in Allergan's periodic public filings with the Securities and Exchange Commission, including but not limited to Allergan's Annual Report on Form 10-K for the year ended December 31, 2015 (certain of such periodic public filings having been filed under the "Actavis plc" name). Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements.
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