AstraZeneca plc : AstraZeneca and Forest Laboratories to initiate phase III clinical trials for ceftazidime/avibactam to treat serious Gram-negative bacterial infections

AstraZeneca and Forest Laboratories, Inc. announced today that ceftazidime/avibactam (CAZ-AVI) will enter phase III trials to investigate efficacy in treating hospitalised patients with serious Gram-negative bacterial infections including Complicated Intra-Abdominal Infections (cIAI) and Complicated Urinary Tract Infections (cUTI). CAZ-AVI combines a broad-spectrum cephalosporin (ceftazidime) and a novel beta-lactamase inhibitor (avibactam, formerly NXL104) to overcome antibiotic-resistance and treat the increasing number of infections resistant to existing therapies.

This study programme will include five phase III trials designed to demonstrate that CAZ-AVI is an effective and well tolerated treatment for patients with cIAI and cUTI including those patients with infections that may be resistant to currently available antibiotics.

This study programme builds on results from two separate CAZ-AVI phase II trials:

• The cIAI Phase II trial showed that the efficacy of CAZ-AVI given with metronidazole in adult patients was similar to meropenem, an established treatment given to patients with Complicated Intra-Abdominal Infections
• The cUTI Phase II trial showed that the efficacy of CAZ-AVI in adult patients was similar to imipenem cilastatin, an established treatment given to patients with Complicated Urinary Tract Infections
• The data from both trials showed that CAZ-AVI in general was well tolerated.

“This new step in the development of CAZ-AVI demonstrates our commitment to help meet the needs of hospitals facing additional healthcare costs linked to a rapid increase of antimicrobial resistant organisms,” said Anders Ekblom, Executive Vice President of Global Medicines Development at AstraZeneca.

Marco Taglietti, MD, Senior Vice President Research & Development, Forest Laboratories and President, Forest Research Institute, said: “We are pleased to move forward with the CAZ-AVI development programme. This combination of a broad-spectrum cephalosporin and a novel beta-lactamase inhibitor has the potential to be effective against bacteria that would otherwise be resistant to antibiotics in patients suffering from serious and potentially life-threatening infections.”

This study programme is designed to support global regulatory filings planned for 2014.

As part of the collaboration, development costs of the treatment will be shared between AstraZeneca and Forest. Forest will have the rights to commercialise CAZ-AVI in North America while AstraZeneca will have rights to commercialise CAZ-AVI in the rest of the world.

The planned phase III development programme is designed to demonstrate that CAZ-AVI is an effective and well tolerated treatment for use in patients with complicated IAI / or complicated UTI Gram negative infections including those where pathogens resistant to commonly used antibiotics (such as extended-spectrum beta-lactamases producing Enterobacteriaceae with resistance to penicillins and third generation cephalosporins) are known or suspected.

Complicated intra-abdominal infections (cIAI). This Phase II trial was a prospective, randomised, double-blind study to estimate the efficacy, safety, and tolerability of CAZ-AVI given with metronidazole vs meropenem in the treatment of 203 adults who were hospitalised with cIAI requiring treatment with intravenous antimicrobial therapy. Patients treated with CAZ-AVI given with metronidazole had a similar high clinical response rate (91.2% patients) compared to those treated with meropenem (93.4% patients).

Complicated urinary tract infections (cUTI). This Phase II trial was a prospective, randomised, single-blind (investigator) study to estimate the efficacy, safety and tolerability of CAZ-AVI vs imipenem plus cilastatin in the treatment of 135 adults who were hospitalised with cUTI requiring treatment with intravenous antimicrobial therapy. Patients treated with CAZ-AVI had a similar high rate for complete pathogen eradication (70.4% patients) when compared to those treated with imipenem and cilastatin (71.4% patients).

In December 2009, AstraZeneca entered into an agreement to acquire Novexel, a private infection research company in France while simultaneously announcing an agreement to collaborate with Forest Laboratories on the future co-development and commercialisation of two late-stage antibiotic development programmes: ceftazidime/avibactam and ceftaroline fosamil/avibactam. These antibiotic combinations utilise Novexel’s novel investigational beta-lactamase inhibitor avibactam to overcome antibiotic-resistance and treat the increasing number of infections resistant to existing therapies. Development costs for CAZ-AVI will be shared between AstraZeneca and Forest.

Forest Laboratories (NYSE: FRX) longstanding global partnerships and track record developing and marketing pharmaceutical products in the United States have yielded its well-established central nervous system and cardiovascular franchises and innovations in anti-infective and respiratory medicine. The Company's pipeline, the most robust in its history, includes product candidates in all stages of development across a wide range of therapeutic areas. The Company is headquartered in New York, NY. To learn more, visit www.FRX.com

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.www.astrazeneca.com

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