Allergan plc. (NYSE: AGN) today announced positive topline results from RECAPTURE 1 and 2, the pivotal Phase III studies evaluating the antibiotic AVYCAZ™ (ceftazidime-avibactam) as a treatment for adult hospitalized patients with complicated urinary tract infections (cUTI), including pyelonephritis.
AVYCAZ consists of a cephalosporin, ceftazidime, an established treatment for serious bacterial infections, and the first and only non-beta lactam beta-lactamase inhibitor, avibactam. The addition of avibactam protects ceftazidime from being broken down by certain beta-lactamases that are produced by these resistant bacteria.
Ceftazidime-avibactam was approved by the US Food and Drug Administration (FDA) as AVYCAZ in February 2015 for the treatment of cUTI including pyelonephritis and complicated intra-abdominal infections (cIAI), in combination with metronidazole, caused by designated susceptible bacteria, including certain Enterobacteriaceae and Pseudomonas aeruginosa for patients 18 years of age and older. AVYCAZ received a priority review based on Phase II data from the company's clinical development program and supporting in vitro data, and as such should be reserved for use in patients who have limited or no alternative treatment options. In the EU, the regulatory submission seeking approval for a 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 2 Phase III studies evaluated the safety and efficacy of AVYCAZ 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 hospitalized 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, AVYCAZ met the objective of statistical non-inferiority compared to doripenem for both the EMA primary and FDA co-primary endpoints.
AVYCAZ was also effective in treating cUTI patients infected with ceftazidime-resistant bacteria.
The most commonly reported adverse events were headache, nausea, constipation and diarrhea. 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 randomization).
"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.
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."
Allergan plans to submit this data as a supplemental New Drug Application (sNDA) to the Food and Drug Administration by the end of 2015.
Ceftazidime-avibactam is being jointly developed with AstraZeneca. Allergan holds the rights to commercialize ceftazidime-avibactam in North America, while AstraZeneca holds the rights to commercialize ceftazidime-avibactam in the rest of the world.
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