Actavis confirmed that the US Food and Drug Administration (US FDA) has accepted for filing Actavis' application for ceftazidime-avibactam, its investigational antibiotic for the treatment of patients with Complicated Urinary Tract Infections (cUTI) and Complicated Intra-Abdominal Infections (cIAI), including those caused by multi-drug resistant Gram-negative bacterial pathogens.
As agreed with FDA, ceftazidime-avibactam was submitted as a 505(b)(2) NDA for the treatment of patients with cIAI and cUTI based on the efficacy and safety of ceftazidime, data from phase II ceftazidime-avibactam studies, robust microbiology and PK/PD analyses. The FDA action date for ceftazidime-avibactam under the Prescription Drug User Fee Act (PDUFA) is expected during Q1 2015.
On August 19, 2014, Actavis announced positive topline results from the single pooled dataset of RECLAIM-1 and -2, pivotal phase III studies evaluating the potential for ceftazidime-avibactam as a treatment for adult patients with cIAI. The company intends to submit the results of the Phase III studies to the FDA as a supplemental New Drug Application (sNDA).
"Today, there exists a serious and unmet need for new options to treat patients suffering from infections due to resistant Gram-negative pathogens, including Carbapenem Resistant Enterobacteriaceae (CRE)," said David Nicholson, senior vice president, Actavis Global Brands R&D. "The acceptance of our filing for approval of ceftazidime-avibactam is a continuation of Actavis' commitment to advancing anti-infective research and development, with a focus on enhancing patient care and outcomes for areas of greatest unmet medical need."
The FDA granted ceftazidime-avibactam Qualified Infectious Disease Product (QIDP) status for its indications of cIAI, cUTI and hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP) on March 11, 2013. The QIDP designation provides certain incentives for the development of new antibiotics, including priority review, eligibility for the FDA's fast track programme, and a five-year extension of exclusivity under the Hatch-Waxman Act.
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 an established and respected 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 offers a differentiated profile versus existing treatment options in serious Gram-negative infections through its coverage of a broad range of species of carbapenem-resistant Enterobacteriaceae (CRE) together with difficult to treat Pseudomonas aeruginosa combined with robust coverage of extended spectrum ß-lactamase (ESBL)-expressing pathogens.
Ceftazidime-avibactam is being jointly developed with Astra Zeneca. Forest Laboratories LLC., a subsidiary of Actavis plc, holds the rights to commercialize ceftazidime-avibactam in North America, while AstraZeneca holds the rights to commercialise 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. Highly resistant Gram-negative bacteria of greatest concern include Enterobacteriaceae that are resistant to ESBLs, including CRE, as well as multidrug-resistant Pseudomonas, two serious health threats that have been identified by the CDC as requiring urgent action. 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, with appendicitis alone affecting approximately 300,000 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), and is becoming increasingly resistant to available antibiotics.