AstraZeneca announced positive top-line results from RECLAIM-1 and RECLAIM-2, the pivotal Phase 3 studies investigating the potential of the antibiotic ceftazidime-avibactam (CAZ-AVI) as a treatment for hospitalized adult patients with complicated intra-abdominal infections.
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 resistant to antibiotics and pose an increasing threat to public health. The addition of avibactam protects ceftazidime from being broken down by beta-lactamases that are produced by resistant bacteria.
The global RECLAIM-1 and RECLAIM-2 Phase 3 studies both evaluated the safety and efficacy of CAZ-AVI, administered intravenously as a two hour infusion (2000 mg / 500 mg) plus metronidazole, compared to meropenem, administered intravenously as a 30 minute infusion (1 g), in hospitalized adult patients with complicated intra-abdominal infections. Data from the RECLAIM-1 and RECLAIM-2 studies were analysed as a single-pooled dataset with the agreement of the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
In the RECLAIM-1 and RECLAIM-2 Phase 3 studies, CAZ-AVI met the objective of statistical non-inferiority compared to meropenem. The primary endpoint was a clinical cure rate 28 to 35 days after randomization (the Test of Cure visit). CAZ-AVI also treated cIAI patients infected with ceftazidime-resistant bacteria as effectively as meropenem.
The adverse event rate for CAZ-AVI in combination with metronidazole was similar to meropenem. The most commonly reported adverse events for CAZ-AVI in combination with metronidazole were diarrhea, nausea, vomiting and fever, which were not unexpected based on the known safety profiles of ceftazidime and metronidazole.
“We are very encouraged by these results which highlight the potential for CAZ-AVI to provide a much-needed new treatment option for serious and life-threatening intra-abdominal infections, especially where antibiotic resistance poses a threat to treatment,” said Briggs Morrison, executive vice president, Global Medicines Development & Chief Medical Officer, AstraZeneca.
Studies are also underway for CAZ-AVI in complicated urinary tract infections (cUTI), nosocomial pneumonia and for the treatment of cIAI and cUTI patients with ceftazidime-resistant infections.
The RECLAIM-1 and RECLAIM-2 Phase 3 studies could form the basis of regulatory submissions seeking approval for a broader range of indications, in line with new EMA guidelines on the evaluation of medicines to treat bacterial infections. EU filing is anticipated in the first quarter of 2015, pending a full analysis of the data from the studies. The results will also be submitted to a scientific meeting in the first half of 2015.
CAZ-AVI is being jointly developed with Forest Laboratories, a wholly-owned subsidiary of Actavis. AstraZeneca holds the global rights to commercialize CAZ-AVI, with the exception of North America where the rights are held by Forest Laboratories.
Date: August 19, 2014
Filed Under: Drug Discovery