AstraZeneca has reported positive topline results from RECAPTURE 1 and RECAPTURE 2, the pivotal Phase III trials evaluating the antibiotic, CAZ-AVI, as a treatment for hospitalised adults with complicated urinary tract infections (cUTI), including pyelonephritis.
CAZ-AVI is a combination of cephalosporin (ceftazidime), an established treatment for serious bacterial infections, and avibactam, a next-generation non-beta lactam beta-lactamase inhibitor.
It is being developed to treat a broad range of gram-negative bacterial infections which are becoming increasingly resistant to antibiotics.
The company noted that the addition of avibactam protects ceftazidime from being broken down by beta-lactamases that are produced by these resistant bacteria.
In the US, where AstraZeneca’s partner Allergan holds the commercialisation rights, CAZ-AVI (AVYCAZ) was approved by the FDA in February 2015 for cUTI and complicated intra-abdominal Infections (cIAI).
The approval of CAZ-AVI to treat cUTI and cIAI patients 18 years of age and older, who currently have limited or no alternative treatment options, was based on a previously submitted new drug application (NDA) with Phase II data.
In the European Union (EU), where AstraZeneca holds the commercialisation rights, the regulatory submission seeking approval for a broad range of indications, was accepted and validated by the European Medicines Agency (EMA) in May 2015 and is currently under review.
AstraZeneca Global Medicines Development vice-president Elisabeth Björk said: "These positive results show the efficacy of CAZ-AVI in treating complicated urinary tract infections, including those resistant to ceftazidime, and further support regulatory submissions to make this medicine available to patients.
"AstraZeneca is committed to addressing the public health challenge posed by emerging infections through our portfolio of innovative antibiotics."
Both the RECAPTURE 1 and RECAPTURE 2 trials evaluated the safety and efficacy of CAZ-AVI, administered intravenously as a two-hour infusion (2000/500mg every eight hours), compared to doripenem, administered intravenously as a 30-minute infusion (500mg every eight hours), in these patients.
In both the trials, CAZ-AVI met the objective of statistical non-inferiority compared to doripenem for both the EMA primary and FDA co-primary endpoints.
In addition, for the EMA primary endpoint, CAZ-AVI was statistically superior (at the 5% level) to doripenem.
The company will provide the RECAPTURE data to the EMA as part of the regulatory review process for the on-going CAZ-AVI marketing authorisation application (MAA).
Image: Macrophages and giant cells in a case of xanthogranulomatous pyelonephritis. Photo: courtesy of Nephron.