AstraZeneca today announced positive topline results from RECAPTURE 1 and RECAPTURE 2, the pivotal Phase III studies evaluating the antibiotic, CAZ-AVI (ceftazidime-avibactam), as a treatment for adult hospitalised patients with complicated Urinary Tract Infections (cUTI), including pyelonephritis.
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 increasingly resistant to antibiotics and pose a threat to public health. 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 (AVYCAZTM) was approved by the Food and Drug Administration (FDA) in February 2015 for cUTI and complicated intra-abdominal Infections (cIAI) for patients 18 years of age and older who currently have limited or no alternative treatment options, based on a previously submitted New Drug Application with Phase II data. In the 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.
The global RECAPTURE 1 and RECAPTURE 2 Phase III studies evaluated the safety and efficacy of CAZ-AVI, administered intravenously as a two-hour infusion (2000/500mg every 8 hours), compared to doripenem, administered intravenously as a 30-minute infusion (500mg every 8 hours), in hospitalised adult patients with cUTI, including pyelonephritis. Data from the studies were analysed as a single- pooled dataset with the agreement of the US FDA and the EMA.
In the RECAPTURE 1 and RECAPTURE 2 Phase III studies, CAZ-AVI met the objective of statistical non-inferiority compared to doripenem for both the EMA primary and FDA co-primary endpoints.
Additionally, for the EMA primary endpoint, CAZ-AVI was statistically superior (at the 5% level) to doripenem.
CAZ-AVI was also effective in treating cUTI patients infected with ceftazidime-resistant bacteria.
The most commonly reported adverse events were headache, nausea, constipation and diarrhoea. No new safety concerns were identified upon review of the most frequent events up to the late follow-up visit (45–52 calendar days after randomisation).
Elisabeth Björk, Vice President, Global Medicines Development, AstraZeneca, 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.”
“We are very pleased by these results, which we plan to submit to the FDA to further support the use of AVYCAZ as a treatment option for patients with these serious and life-threatening complicated urinary tract infections,” said David Nicholson, Executive Vice President & President, Global Brands R&D at Allergan.
The RECAPTURE data will be provided to the EMA as part of the regulatory review process for the on-going CAZ-AVI Marketing Authorisation Application.