Allergan plc, a leading global pharmaceutical company, announced that the US Food and Drug Administration (FDA) has approved the company's supplemental New Drug Application (sNDA) to update the label for avycaz (ceftazidime and avibactam) with clinical data from two phase 3 trials supporting the indication to treat patients with complicated urinary tract infections (cUTI), including pyelonephritis, caused by designated susceptible gram-negative microorganisms.
In trial 1, known as recapture, avycaz was non-inferior to doripenem with regard to both primary endpoints. In trial 2, known as reprise, avycaz demonstrated a higher combined clinical and microbiological cure rate vs. best available therapy (BAT), including meropenem, imipenem, doripenem, and colistin. Additionally, both trials included a subset of patients with infections caused by pathogens producing certain ESBL groups and AmpC beta-lactamases in which the clinical and microbiological cure rates were similar to the overall results.
The prevalence of infections caused by resistant gram-negative bacteria, specifically extended spectrum beta-lactamase (ESBL) and Klebsiella pneumoniae carbapenamase (KPC)-producing carbapenem-resistant Enterobacteriaceae (CRE), and resistant Pseudomonas aeruginosa have steadily increased in recent years; this has led the U S Centers for Disease Control and Prevention (CDC) to classify these pathogens as urgent and serious public health threats, as there are very limited treatment options.
"Gram-negative pathogens are among the most urgent antibiotic resistance threats and cause more than 40,000 resistant infections in the U.S. alone each year," said David Nicholson, Ph.D., chief r&d officer, Allergan. "This new sNDA approval for avycaz is based on a large clinical database, comprising data from more than 1,300 patients with cUTI across Phase 3 studies, including a number of patients with infections due to ceftazidime non-susceptible (CAZ-NS) pathogens. It provides physicians with further clinical evidence that will assist them in making informed treatment decisions for their patients with cUTI, including those with difficult to treat pathogens."
"The successful cumulative Phase 3 cUTI studies further validate the initial FDA approval of avycaz based on Phase 2 data. The inclusion of the reprise data in the label represents a significant advancement in the available data to support efficacy in cUTI patients infected with challenging pathogens, including certain ESBL and KPC-producing Enterobacteriaceae, reinforcing Allergan's leadership in responding to some of the most challenging infections facing our society."
Avycaz was first approved in the U S in February 2015 for the treatment of adult patients with complicated intra-abdominal infections (cIAI), in combination with metronidazole, and cUTI, including pyelonephritis, caused by designated susceptible pathogens, including certain Enterobacteriaceae and Pseudomonas aeruginosa. In June 2016, the FDA approved the addition of Phase 3 cIAI clinical data to the label that evaluated the safety and efficacy of avycaz, in combination with metronidazole in cIAI patients, including subsets of patients with infections caused by CAZ-NS pathogens and pathogens producing certain ESBLs.
Avycaz has 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). 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.
Ceftazidime and avibactam is being jointly developed with Pfizer. Allergan holds the rights to commercialize ceftazidime and avibactam in North America under the brand name avycaz, while Pfizer holds the rights to commercialize the combination in the rest of the world under the brand name Zavicefta.
Allergan plc, headquartered in Dublin, Ireland, is a bold, global pharmaceutical company and a leader in a new industry model - Growth Pharma. Allergan is focused on developing, manufacturing and commercializing branded pharmaceuticals, devices and biologic products for patients around the world.
Allergan markets a portfolio of leading brands and best-in-class products for the central nervous system, eye care, medical aesthetics and dermatology, gastroenterology, women's health, urology and anti-infective therapeutic categories.
Allergan is an industry leader in Open Science, the company's r&d model, which defines our approach to identifying and developing game-changing ideas and innovation for better patient care. This approach has led to Allergan building one of the broadest development pipelines in the pharmaceutical industry with 70+ mid-to-late stage pipeline programs in development.
Allergan's snda for avycaz gets us fda nod, to include new phase iii data in patients with cuti, including pyelonephritis
