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FDA approves new Zerbaxa indication for bacterial pneumonia
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The FDA has approved a new indication for Zerbaxa for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia in patients aged 18 years and older.
Zerbaxa (Merck) is an antibacterial combination product for IV infusion consisting of the cephalosporin antibacterial drug ceftolozane sulfate and the beta-lactamase inhibitor tazobactam sodium.
The FDA initially approved Zerbaxa in 2014 for the treatment of complicated intra-abdominal infections and for complicated urinary tract infections. The expanded approval is for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by the following susceptible gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Serratia marcescens, according to a press release issued by Merck.
According to a recent publication by the Foundation for the NIH Biomarkers Consortium, ventilated patients with hospital-acquired bacterial pneumonia have a higher rate of mortality (39%) than those with ventilator-associated bacterial pneumonia (27%). Moreover, P. aeruginosa is the most common gram-negative pathogen in hospital-acquired and ventilator-associated bacterial pneumonia and is becoming increasingly difficult to treat, according to information in the release.
“Pneumonia in ventilated patients remains a significant challenge. The new indication for Zerbaxa gives us another important tool in our toolkit for dealing with a complicated disease with high morbidity and mortality for which we have very few new options for antimicrobial resistance,” Andrew Schorr, MD, head of pulmonary, critical care and respiratory services, Medstar Washington Hospital Center, Washington, D.C., told Healio Pulmonology.
The expanded indication for pneumonia was based on results of the phase 3 ASPECT-NP trial, which compared Zerbaxa with meropenem. The trial enrolled 726 adults (mean age, 62 years; 83% white, 71% men) with ventilated nosocomial pneumonia who were randomly assigned to receive 3 g ceftolozane/tazobactam or 1 g meropenem via IV infusion over 1 hour every 8 hours for 8 to 14 days. All patients were intubated and on mechanical ventilation at randomization.
“The ASPECT-NP study is unique among pneumonia studies because all of the patients enrolled were ventilated, while in many of the other hospital-acquired infection studies the ventilated population is between one-third and two-thirds of patients. The study enrolled a particularly sick patient population,” Yoav Golan, MD, attending physician and associate professor of medicine at Tufts University School of Medicine, told Healio Pulmonology.
As previously reported by Infectious Disease News, Zerbaxa was noninferior to meropenem in this population, with similar rates of 28-day all-cause mortality (24% vs. 25.3%) and clinical response at test of cure 7 to 14 days after the end of therapy (54.4% vs. 53.3%). Elevated liver enzyme levels, renal impairment or failure, and diarrhea were the most common adverse observed reactions in the ASPECT-NP trial, according to an FDA press release.
The ASPECT-NP trial “was anticipated for a long time,” Golan said. “Zerbaxa has the potential to improve care for this subgroup of patients with pneumonia who present very ill and whose lives depend on adequate and empiric treatment.”
Zerbaxa received the FDA’s Qualified Infectious Disease Product designation for the treatment of hospital-acquired ventilator-assisted bacterial pneumonia. As part of this designation, the new application was granted priority review.
“A key global challenge we face as a public health agency is addressing the threat of antimicrobial-resistant infections,” FDA Principal Deputy Commissioner Amy Abernethy, MD, PhD, stated in the FDA release. “Hospital-acquired and ventilator-associated bacterial pneumonia are serious infections that can result in death in some patients. New therapies to treat these infections are important to meet patient needs because of increasing antimicrobial resistance. That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections.”
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Yoav Golan, MD, is attending physician and associate professor of medicine at Tufts University School of Medicine.
Andrew Schorr, MD, is head of pulmonary, critical care and respiratory services at Medstar Washington Hospital Center.
Disclosure: Abernathy is principal deputy commissioner at the FDA. Golan reports he receives research grants from Allergan and Merck and is an advisor/consultant/speaker for Achaogen, Allergan, Cutis, Melinta, Merck, Paratek, Pfizer, Sanofi, Seres and Tetraphase. Schorr reports he has served as a consultant to Merck.
Editor’s note: This article was updated on June 4, 2019, with quotes from Andrew Schorr, MD, and Yoav Golan, MD.