FDA Approves Allergan's Ceftazidime, Avibactam for HABP, VABP

This is the first gram-negative antibiotic approved in the US in over 15 years to treat HABP, VABP.

The US Food and Drug Administration (FDA) approved Allergan’s supplemental new drug application (sNDA), expanding the approved use of ceftazidime and avibactam (AVYCAZ) to include the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by 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.

The expanded use is based on positive results from a pivotal phase 3 study, REPROVE, which evaluated the efficacy and safety of AVYCAZ for the treatment of adult patients with HABP/VABP.

In October 2017, the sNDA received priority review based on the qualified infectious disease product designation for the new indication.

HABP/VABP is currently the second most common type of nosocomial infection in the US and is associated with high mortality and morbidity.

“Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia are among the most serious Gram-negative infections, and are increasingly caused by difficult to treat pathogens, leading to high morbidity and mortality, especially in the ICU and hospital, and increased economic burden,” David Nicholson, PhD, Chief Research and Development Officer, Allergan, told MD Magazine.

In the REPROVE study, 870 hospitalized adult patients with HABP or VABP were randomized to receive either 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) intravenously every 8 hours, or meropenem 1 gram intravenously every 8 hours, for 7—14 days of therapy.

The primary efficacy endpoint was 28-day all-cause mortality in the intent-to-treat population. Findings concluded 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% in patients treated with AVYCAZ versus 8.3% in meropenem treated patients.

“Clinical efficacy along with patient safety are critical priorities to clinicians managing serious Gram-negative bacterial infections,” Jose Vazquez, MD, FIDSA, division chief, and professor of medicine infectious diseases, Medical College of Georgia/Augusta University, said in a statement. “We are thrilled to have a new option available to treat HABP/VABP, some of the most challenging Gram-negative infections in the hospital setting.”

In the study, the overall safety profile observed was consistent with current product labeling. The most common adverse effects ≥ 5% were diarrhea and vomiting.

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

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