The Food and Drug Administration (FDA) has approved Fetroja (cefiderocol; Shionogi) for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Enterobacter cloacae complex. The treatment is indicated for patients aged ≥18 years 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 approval was based on 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 cefiderocol was noninferior to the comparator. In the study, 72.6% of patients in the cefiderocol arm met the primary end point (composite of clinical cure and microbiologic eradication at Test of Cure) vs 54.6% in the imipenem-cilastatin arm.
With regard to safety, the most commonly reported treatment-emergent adverse reactions included diarrhea, infusion site reactions, constipation, rash, candidiasis, cough, elevations in liver tests, headache, hypokalemia, nausea, and vomiting.
“Today’s approval provides an additional treatment option for patients with cUTIs who have limited or no alternative treatment options,” said John Farley, MD, MPH, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research. “A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. This approval represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections.”
Fetroja is supplied as 1g of cefiderocol as lyophilized powder for reconstitution in single-dose vials. The treatment is administered via intravenous infusion. The Company expects to make Fetroja available in early 2020.
For more information visit shionogi.com.