Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia are life-threatening hospital-related pulmonary infections that can particularly impact patients who are already dealing with severe underlying medical conditions.
It didn’t take long for the U.S. Food and Drug Administration (FDA) to approve a supplemental New Drug Application for Merck’s Zerbaxa.
In April, the pharma giant announced it had filed the sNDA based on the results from the Phase III ASPECT-NP trial for adult patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by certain bacteria. Trial results showed that Zerbaxa (ceftolozane and tazobactam) was on par with meropenem as a treatment for those patients. Merck initially reported the results of the Phase III trial in September, which set the stage for its potential approval for pneumonia patients.
The FDA swiftly moved to approve the treatment on a Priority Review. Merck noted that Zerbaxa should only be used to treat or prevent infections caused by the bacteria for which it was approved, including Enterobacter cloacae, Escherichia coli, Hemophilus influenza, Klebsiella oxytoca, Klebsiella pneumonia, Proteus mirabilis, Pseudomonas aeruginosa and Serratia marcescens.
Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia are life-threatening hospital-related pulmonary infections that can particularly impact patients who are already dealing with severe underlying medical conditions. There is a high mortality rate associated with these illnesses. A recent report from the Foundation for the National Institutes of Health Biomarkers Consortium noted that ventilated patients with HABP have a 39% higher rate of mortality than those with VABP, 27%. In addition, Pseudomonas aeruginosa is the most common Gram-negative pathogen in HABP/VABP and is becoming increasingly difficult to treat. Merck said that 100% of the patients involved with the Phase III trial were on mechanical ventilation.
Amy Abernathy, principal deputy commissioner at the FDA, said the threat of antimicrobial-resistant infections is a key global challenge for public health agencies. HABP/VABP are serious infections that can be fatal, she said and noted that new therapies to treat these infections are essential due to increasing microbial resistance.
In the Phase III ASPECT-NP study, 726 patients were randomized 1:1 to receive an investigational 3g dose of Zerbaxa or 1g of meropenem, administered intravenously every eight hours for eight to 14 days. The median age of the patients in the trial was 62, Merck said. Approximately 13% of patients were failing their current antibacterial drug therapy for HABP/VABP, and bacteremia was present at baseline in 15% of patients. Many of the patients had key comorbidities, including diabetes, congestive heart failure and COPD.
As noted before, all of the patients were intubated and mechanically ventilated and the vast majority of the trial patients were treated in the intensive care unit, Merck said. Trial results showed that after 28 days in the intent-to-treat population, Zerbaxa was non-inferior to meropenem. In the microbiologically evaluable (ME) population in patients with a Gram-negative pathogen at baseline, clinical cure rates were 75.2% and 66.7% for Zerbaxa and meropenem, respectively, Merck said. Also, microbiologic response rates were 69.9% and 62.4% for Zerbaxa and meropenem.
“We are grateful to all of the patients who participated in the studies which led to the approval of Zerbaxa for the treatment of HABP/VABP,” Roy Baynes, senior vice president and head of global clinical development and chief medical officer at Merck Research Laboratories, said in a statement. “This approval reflects Merck’s longstanding commitment to helping alleviate the burden of infectious diseases, including serious infections caused by Gram-negative pathogens.”
