General Information

Fetroja (cefiderocol) is a cephalosporin antibacterial.

Fetroja is specifically indicated for the following:

patients 18 years of age or older who have limited or no alternative treatment options for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Enterobacter cloacae complex.

patients 18 years of age or older with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by the following susceptible Gram-negative microorganisms: Acinetobacter baumannii complex, Escherichia coli, Enterobacter cloacae complex, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens.

Fetroja is supplied as an injection for intravenous administration. The recommended dosage of Fetroja is 2 grams administered every 8 hours by intravenous (IV) infusion over 3 hours in adults with a creatinine clearance (CLcr) of 60 to 119 mL/min. Dosage adjustment is recommended for patients with CLcr less than 60 mL/min or for patients with CLcr 120 mL/min or greater. Please see drug label for specific dosing recommendations. The recommended duration of treatment with Fetroja is 7 to 14 days. The duration of therapy should be guided by the severity of infection and the patient’s clinical status for up to 14 days.

Mechanism of Action

Fetroja (cefiderocol) is a cephalosporin antibacterial with activity against Gram-negative aerobic bacteria. Cefiderocol functions as a siderophore and binds to extracellular free ferric iron. In addition to passive diffusion via porin channels, cefiderocol is actively transported across the outer cell membrane of bacteria into the periplasmic space using a siderophore iron uptake mechanism. Cefiderocol exerts bactericidal action by inhibiting cell wall biosynthesis through binding to penicillin-binding proteins (PBPs).

Indication 1 - the treatment of complicated urinary tract infections

approved November 2019

Clinical Trial Results

The FDA approval of Fetroja for cUTI's was based on data from the pivotal APEKS-cUTI study, a multinational, multicenter, double-blind clinical trial that evaluated the efficacy and safety of Fetroja versus imipenem/cilastatin (IPM/CS) in patients with cUTI. Study results showed the response rates for the composite endpoint of microbiological eradication and clinical response at the test of cure (TOC) were significantly higher in the Fetroja arm compared to the IPM/CS arm. In the study, 72.6% (183/252) of patients in the Fetroja arm met the primary endpoint versus 54.6% (65/119) in the IPM/CS arm at TOC. The adjusted difference between the groups was 18.58%. Clinical response rates at the TOC visit were similar between Fetroja and IPM/CS.

Indication 2 - the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia

approved September 2020

Clinical Trial Results

The FDA approval of Fetroja for HABP/VABP was based on APEKS-NP (Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Stenotrophomonas maltophilia in Nosocomial Pneumonia), a multinational, multicenter, double-blind, randomized, trial designed to evaluate the efficacy and safety of Fetroja for the treatment of nosocomial pneumonia including HABP, VABP, and HCABP caused by Gram-negative pathogens. Patients were randomized on a 1:1 basis to receive Fetroja administered by intravenous infusion of two grams over a three-hour period every eight hours or high-dose extended-infusion meropenem administered as two grams over a three-hour period every eight hours, for seven to 14 days in the hospital. Linezolid was additionally administered for at least five days in both arms to provide coverage for methicillin-resistant Staphylococcus aureus (MRSA), and for Gram-positive bacteria in the Fetroja group. The trial met the primary endpoint of non-inferiority to high-dose meropenem, infused over three hours. At Day 14, all-cause mortality (ACM) in the modified intent-to-treat population was 12.4% for Fetroja (18/145) and 12.2% for high-dose meropenem (18/147), respectively. Key secondary endpoints were also reached, including clinical outcomes at test of cure (TOC) defined as seven days after treatment, and Day 28 ACM: Clinical outcome at TOC: 64.8% (94/145) Fetroja versus 66.7% (98/147) meropenem high dose. Day 28 ACM: 22.1% (32/145) Fetroja versus 21.1% (31/147) meropenem high dose.