This filing will add important new clinical data to the current label from two Phase 3 trials evaluating the safety and efficacy of AVYCAZ, in combination with metronidazole, for the treatment of complicated intra-abdominal infections (cIAI), including patients with infections due to ceftazidime-nonsusceptible (CAZ-NS) pathogens.
The FDA granted priority review status to this application based on the previous Qualified Infectious Disease Product (QIDP) designation for AVYCAZ. Allergan expects the Agency to take action on the filing in the second quarter of 2016.
AVYCAZ was first approved in the U.S. in February 2015 for the treatment of adult patients with cIAI, in combination with metronidazole, and complicated urinary tract infections (cUTI), including pyelonephritis, caused by designated susceptible bacteria, including certain Enterobacteriaceae and Pseudomonas aeruginosa.
This original approval was based on Phase 2 data from the company’s clinical development program and supporting in vitro data, and as a result, the current labeling denotes AVYCAZ should be reserved for use in cIAI and cUTI patients who have limited or no alternative treatment options.
Allergan president and executive vice president of global R&D David Nicholson said: "Since its approval, AVYCAZ has provided physicians with a treatment option to address complicated intra-abdominal infections caused by certain Gram-negative pathogens for which physicians currently have limited or no options.
"This acceptance is encouraging, as the inclusion of full Phase 3 clinical data to the label further demonstrates the safety and efficacy of AVYCAZ in difficult-to-treat infections and provides physicians further validation of the drug’s spectrum of activity against pathogens of greatest concern."
"We look forward to working with the FDA in the coming months to add these data to the AVYCAZ label. We are committed to the ongoing development of our anti-infective portfolio to help the healthcare community respond effectively to serious infections," Nicholson said.
The application included results from two Phase 3 studies, which evaluated the efficacy and safety of AVYCAZ, in combination with metronidazole, for the treatment of patients with cIAI, including patients with infections due to Gram-negative pathogens that met pre-specified criteria for pathogens resistant to ceftazidime alone but susceptible to AVYCAZ. In these studies, clinical cure rates at the Test of Cure (TOC) time point met the primary endpoint of statistical non-inferiority to meropenem.
AVYCAZ has demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (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). AVYCAZ 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.
Phase 3 studies evaluating the safety and efficacy of AVYCAZ for the treatment of cUTI have been completed and the data is being analyzed for submission later this year.
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.
About AVYCAZ
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-ß lactam ß-lactamase inhibitor.
The addition of avibactam to ceftazidime protects ceftazidime from breakdown by certain ß-lactamases. AVYCAZ offers a differentiated profile in the treatment of cIAI, (in combination with metronidazole, and cUTI through its in vitro activity against Enterobacteriaceae, including those that produce certain ESBL and KPC, and difficult-to-treat Pseudomonas aeruginosa.