Regulatory Affairs

FDA approves Avycaz to treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia

Published 02 February 2018

The US Food and Drug Administration (FDA) has approved Allergan's supplemental new drug application (sNDA) to expand the approved use of Avycaz (ceftazidime and avibactam) to include the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).

It was approved to treat HABP/VABP caused by the following susceptible Gram-negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae in patients 18 years of age or older.

This expanded use is based on positive results from a pivotal Phase 3 study evaluating the efficacy and safety of AVYCAZ for the treatment of adult patients with HABP/VABP. The sNDA received priority review from FDA based on the Qualified Infectious Disease Product (QIDP) designation for the HABP/VABP indication.

Certain types of Gram-negative bacteria have become increasingly resistant to available antibiotics, resulting in increased illness and death as well as contributing to escalating healthcare costs.1 New strategies to fight these challenging infections have been long-awaited by the medical community.

Allergan chief research and development officer Dr David Nicholson said: "Healthcare providers in the U.S. have not had access to a new treatment option for patients with HABP/VABP due to Gram-negative bacteria in over 15 years.”

"Gram-negative pathogens are some of the most pressing antibiotic resistance threats and cause more than 40,000 resistant infections in the U.S. annually. Today's action by the FDA is further evidence of Allergan's commitment to improving outcomes and meeting critical needs in patients with life-threatening infectious diseases."

This is the third therapeutic indication for AVYCAZ. AVYCAZ was first approved in February 2015 in the U.S. for the treatment of adult patients with complicated intra-abdominal infections (cIAI), in combination with metronidazole, and in 2017 for complicated urinary tract infections (cUTI), including pyelonephritis, caused by designated susceptible Gram-negative bacteria, including certain Enterobacteriaceae and Pseudomonas aeruginosa.

A total of 870 hospitalized adult patients with HABP or VABP were randomized and received trial medications in a pivotal Phase 3, multinational, double-blind trial (REPROVE) comparing AVYCAZ 2.5 g (ceftazidime 2 grams and avibactam 0.5 grams) intravenously every 8 hours to meropenem 1 gram intravenously every 8 hours, for 7 to 14 days of therapy.

Study medication dosages were adjusted per renal function. The protocol allowed for administration of prior and concomitant systemic antibacterial therapy for patients with proven or suspected Gram-positive or drug resistant infections.

Clinical efficacy was evaluated in the intent-to treat (ITT) population, which included all randomized patients who received study drug. Overall, 379 (43.6%) patients were ventilated at enrollment, including 290 (33.3%) patients with VABP and 89 (10.2%) with ventilated-HABP. Bacteremia at baseline was present in 4.8% of patients.

The primary efficacy endpoint of the study was 28-day all-cause mortality (28 to 32 days after randomization) in the ITT population. The study successfully demonstrated that AVYCAZ was non-inferior to meropenem with respect to the primary endpoint based on a 10% non-inferiority margin; the 28-day all-cause mortality rate was 9.6% (42/436) in patients treated with AVYCAZ compared with 8.3% (36/434) in meropenem treated patients (treatment difference of 1.5%; 95% confidence interval [CI]: -2.4, 5.3).  

AVYCAZ is a fixed-dose combination antibacterial indicated for the treatment of HABP/VABP, cIAI (in combination with metronidazole), and cUTI caused by designated susceptible Gram-negative microorganisms in patients 18 years or older. AVYCAZ consists of a combination of avibactam and ceftazidime.

Avibactam is a first-in-class non-beta-lactam beta-lactamase inhibitor which protects ceftazidime against degradation by certain beta-lactamases. Avibactam does not decrease the activity of ceftazidime against ceftazidime-susceptible organisms. Ceftazadime is a third-generation cephalosporin with a well-established efficacy and safety profile.

Ceftazidime and avibactam is being jointly developed with Pfizer. Allergan holds the rights to commercialize ceftazidime and avibactam in North America under the brand name AVYCAZ, while Pfizer holds the rights to commercialize the combination in the rest of the world under the brand name ZAVICEFTA®.



Source: Company Press Release