The Food and Drug Administration (FDA)’s Antimicrobial Drugs Advisory Committee voted 14 to 2 in favor of approval of cefiderocol for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, in patients with limited or no alternative treatment options.
Cefiderocol, a novel siderophore cephalosporin, penetrates the outer cell membrane of Gram-negative pathogens by binding to ferric iron. It is then actively transported into the cells via the bacterial iron transporters, allowing for higher concentrations in the periplasmic space where it binds to receptors and inhibits cell wall synthesis.
The New Drug Application (NDA) submission included data from an active-controlled noninferiority trial in which cefiderocol was compared with imipenem-cilastatin in patients with cUTI. Results of the study showed that the investigational treatment was noninferior to the comparator.
In addition, the application included data from a descriptive study comparing cefiderocol to best available therapy in patients with infections (hospital acquired bacterial pneumonia/ventilator associated bacterial pneumonia, cUTI, and bloodstream infections/sepsis) due to carbapenem-resistant organisms. In this study, all-cause mortality was found to be higher in the cefiderocol group compared with the best available therapy group. However, while a greater percentage of patients in the cefiderocol group had infection-related death, an imbalance in death due to underlying comorbidities was noted in the trial.
“Whether this difference in mortality is a chance finding or truly reflects a deficit in the activity of cefiderocol in critically ill patients is unclear,” the panel stated in meeting documents.
Top-line results from the ongoing APEKS-NP study were also included in the package, however these findings were not verified by the FDA. Results from the study showed that cefiderocol was noninferior to meropenem with regard to all-cause mortality in adult patients with nosocomial pneumonia.
Although not bound by the committees’ recommendations, the FDA does take them into consideration when making decisions on approval. The Agency has assigned a Prescription Drug User Fee Act (PDUFA) target date of November 14, 2019 for the application. If approved, the product would be marketed under the brand name Fetroja.
For more information visit fda.gov.
This article originally appeared on MPR