FDA OKs Updated Label for Avycaz in Complicated UTI

Megan Brooks


February 01, 2017

The US Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) to update the label for ceftazidime-avibactam (Avycaz, Allergan PLC) to include data from two phase 3 trials, "supporting the indication to treat patients with complicated urinary tract infections (cUTI), pyelonephritis, caused by designated susceptible Gram-negative microorganisms," the company has announced.

In the RECAPTURE study of adults with cUTI, Avycaz was noninferior to doripenem (Doribax, Shionogi Inc) on the dual primary endpoints of patient-reported symptomatic response at day 5 and combined patient-reported symptomatic response and microbiological cure at the test of cure (TOC) visit in the microbiologically modified intent-to-treat population, the company said.

The symptomatic response rate at day 5 was 70.2% with Avycaz compared with 66.2% with doripenem, a treatment difference of 4.0% (95% confidence interval [CI], -2.4 to 10.4). The combined symptomatic and microbiological response rate at TOC was 71.2% with Avycaz vs 64.5% with doripenem, a treatment difference of 6.7% (95% CI, 0.3 - 13.1).

In the REPRISE study, Avycaz demonstrated a higher combined clinical and microbiological cure rate in comparison with best available therapy, including meropenem (Merren, AstraZeneca), imipenem (Primaxin, Merck), doripenem, and colistin (Coly-Mycin S, Enda Pharmaceuticals. Avycaz was also effective in treating a subset of cUTI patients with ceftazidime nonsusceptible pathogens, the company said.

Both trials included a subset of patients with infections caused by pathogens producing certain extended-spectrum beta-lactamase (ESBL) groups and AmpC beta-lactamases in which the clinical and microbiological cure rates were similar to the overall results, they note.

"Gram-negative pathogens are among the most urgent antibiotic resistance threats and cause more than 40,000 resistant infections in the US alone each year," David Nicholson, PhD, Allergan's head of research and development, said in a news release.

"This new sNDA approval for Avycaz is based on a large clinical database, comprising data from more than 1300 patients with cUTI across phase 3 studies, including a number of patients with infections due to ceftazidime nonsusceptible (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," said Dr Nicholson.

"The successful cumulative phase 3 cUTI studies further validate the initial 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," he added.

Avycaz is indicated for the treatment of patients aged 18 years and older with cUTI, including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii complex, Proteus mirabilis, and Pseudomonas aeruginosa.

Avycaz is also FDA-approved in combination with metronidazole (multiple brands) for treatment of complicated intra-abdominal infections caused by the following susceptible Gram-negative microorganisms: E coli, K pneumoniae, P mirabilis, E cloacae, Klebsiella oxytoca, C freundii complex, and P aeruginosa in patients aged 18 years and older.

"To reduce the development of drug-resistant bacteria and maintain the effectiveness of Avycaz and other antibacterial drugs, Avycaz should be used to treat only indicated infections that are proven or strongly suspected to be caused by susceptible bacteria," the company said.

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