Date: 2015-10-10
Type of information: Presentation of results at a congress
phase:
Announcement: presentation of results at IDWeek
Company: Allergan (Ireland)
Product: ceftazidime/avibactam (CAZ-AVI)
Action
mechanism: antibiotic/cephalosporine/beta-lactamase inhibitor. CAZ-AVI consists of a cephalosporin (ceftazidime), an established treatment for serious bacterial infections, and a next generation non-beta lactam beta-lactamase inhibitor (avibactam). CAZ-AVI is being developed to treat a broad range of Gram-negative bacterial infections which are becoming resistant to antibiotics and pose an increasing threat to public health. The addition of avibactam protects ceftazidime from being broken down by beta-lactamases that are produced by resistant bacteria. CAZ-AVI is being jointly developed with Forest Laboratories, a wholly-owned subsidiary of Actavis, now Allergan.
Disease: complicated urinary tract infections (cUTI)
Therapeutic area: Infectious diseases
Country:
Trial details:
Latest
news: * On October 10, 2015, researchers presented data at IDWeek from the International Network for Optimal Resistance Monitoring (INFORM) program, one of the largest ongoing surveillance programs in the United States . This program is part of a research effort developed and supported by Allergan that monitors the prevalence of resistant bacteria and changing trends of resistance, as well as the in vitro activity of antibiotics against these pathogens. The INFORM data presented at IDWeek reported that the antibiotic Avicaz™ (ceftazidime and avibactam) demonstrated potent in vitro activity against certain common Enterobacteriaceae pathogens isolated from patients with complicated urinary tract infections (cUTI) in U.S. hospitals, including those caused by certain KPC-producing Gram-negative bacteria, meropenem non-susceptible Klebsiella pneumoniae and isolates demonstrating an extended-spectrum beta-lactamase (ESBL)-phenotype. These pathogens are often resistant to multiple antimicrobial agents, which may be important when limited alternative treatment options are available. This analysis also found AVYCAZ was highly active against certain Klebsiella species resistant to other beta-lactam antibiotics, as well as Pseudomonas aeruginosa, including the majority of isolates non-susceptible to meropenem. Ceftazidime and avibactam was approved by the FDA as Avicaz™ in February 2015 for the treatment of cUTI including pyelonephritis and complicated intra-abdominal infections (cIAI), in combination with metronidazole, caused by designated susceptible bacteria, including certain Enterobacteriaceae and Pseudomonas aeruginosa for patients 18 years of age and older. As only limited clinical safety and efficacy data for Avicaz™ are currently available, reserve Avicaz™ for use in patients who have limited or no alternative treatment options.
This approval was based in part on data that found Avicaz™ demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and ESBLs of the following groups: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPCs), AmpC, and certain oxacillinases (OXA). AVYCAZ also demonstrated in vitro activity against Pseudomonas aeruginosa in the presence of some AmpC beta-lactamases, and certain strains lacking outer membrane porin (OprD). Avicaz™ is not active against bacteria that produce metallo-beta lactamases and may not have activity against Gram-negative bacteria that overexpress efflux pumps or have porin mutations.
The INFORM data, presented in a poster titled, \"Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Tested Against Gram-negative Organisms Isolated from Urinary Tract Infections (UTI): Results from the International Network for Optimal Resistance (INFORM) Program,\" evaluated 7,262 unique patient organisms from patients with UTIs treated at 71 U.S. medical centers between 2012 and 2014. Susceptibility testing was performed for ceftazidime and avibactam, ceftazidime alone, meropenem and piperacillin-tazobactam by reference broth microdilution methods. Enterobacteriaceae with an ESBL phenotype were evaluated for the presence of genes encoding ESBLs, KPC, metallo and transferable AmpC enzymes using a microarray-based assay.
Ceftazidime and avibactam is co-developed with partner AstraZeneca . AstraZeneca has filed a variation to the Marketing Application in the EU seeking approval for similar indications.
