The US Food and Drug Administration's Anti-Infective Drugs Advisory Committee has voted to recommend approval of Actavis' New Drug Application (NDA) for ceftazidime-avibactam, an investigational antibiotic being developed to treat hospitalized patients when limited or no treatment options are available for complicated intra-abdominal infections (cIAI) (in combination with metronidazole) and complicated urinary tract infections (cUTI) (including acute pyelonephritis) caused by Gram-negative pathogens.

The committee found the scientific and clinical evidence submitted by Cerexa, Inc., a wholly owned subsidiary of Actavis, adequately demonstrated the safety and efficacy of ceftazidime-avibactam in the treatment of the proposed cIAI and cUTI indications. The committee voted not to recommend approval of the combination for hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP) and bacteremia.

"We are pleased with the committee's positive recommendation for ceftazidime-avibactam. It reinforces our belief in the safety and efficacy of the compound and its potential to address significant unmet needs as a new treatment option for patients with serious and life-threatening infections," said David Nicholson, senior vice president, global brands research and development, Actavis. "As public health officials continue to sound the alarm on antibiotic-resistant infections, Actavis remains committed to advancing the ceftazidime-avibactam clinical development program, including for the combination of hospital acquired bacterial pneumonia (HABP)/ ventilator-associated bacterial pneumonia (VABP) and bacteremia, and working closely with the FDA as it completes its review of our New Drug Application."

Ceftazidime-avibactam inhibits a broad range of ß- lactamases, including Class A (Extended-Spectrum ß-Lactamases and Klebsiella pneumoniae carbapenemase), Class C (AmpC) and some class D enzymes produced by Gram-negative pathogens that are encountered in the hospital setting and involved in some of the most serious infections like cIAI and cUTI.

The Advisory Committee recommendation is not binding on the FDA, which makes the final decision regarding approval. Actavis expects FDA action on its NDA for ceftazidime-avibactam during the first quarter of 2015.

Ceftazidime-avibactam is an investigational antibiotic being developed to treat serious Gram-negative bacterial infections. It consists of ceftazidime, a third-generation, antipseudomonal cephalosporin that is a well-established treatment for serious Gram-negative bacterial infections, and avibactam, a next generation, non-ß lactam ß-lactamase inhibitor.

The addition of avibactam to ceftazidime protects ceftazidime from breakdown by ß-lactamases. Ceftazidime-avibactam addresses important needs in the treatment of Gram-negative infections, including those caused by extended spectrum ß-lactamase-producing Gram-negative pathogens, carbapenem-resistant Enterobacteriaceae (CRE) and multidrug-resistant (MDR) Pseudomonas aeruginosa.

Ceftazidime-avibactam is being jointly developed with Astra Zeneca. Actavis 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.

Gram-negative bacteria are highly adaptive pathogens that can develop resistance through several mechanisms and can pass along genetic materials that allow other bacteria to become drug-resistant as well. The Centers for Disease Control and Prevention (CDC) has identified antibiotic resistance as a threat in the US and has categorized the level of concern for carbapenem-resistant Enterobacteriaceae (CRE) as "urgent" and for both Extended spectrum ß-lactamase producing Enterobacteriaceae (ESBLs) and MDR P. aeruginosa as "serious." Many of these Gram-negative pathogens are particularly worrisome because they are becoming resistant to nearly all drugs, including the carbapenems, often considered the last line of defense in these challenging infections.

Gram-negative bacteria are common causes of intra-abdominal infections, urinary tract infections, and healthcare-associated (nosocomial) pneumonia and bloodstream infections.

Complicated intra-abdominal infections are a considerable problem, affecting approximately 1.1 million patients each year. Intra-abdominal infections are the second most common cause of infectious mortality in the intensive care unit.

Complicated urinary tract infections are also often caused by Gram-negative pathogens. Escherichia coli (E. coli) is one of the common organisms causing urinary tract infections (UTIs), affecting 2.9 million patients each year, and is becoming increasingly resistant to available antibiotics.

Actavis plc, headquartered in Dublin, Ireland, is a unique specialty pharmaceutical company focused on developing, manufacturing and commercializing high quality affordable generic and innovative branded pharmaceutical products for patients around the world.