Exblifep Approved for Complicated UTI, Including Pyelonephritis

The Food and Drug Administration (FDA) has approved Exblifep^® (cefepime/enmetazobactam) for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTIs), including pyelonephritis.

Exblifep is a combination product that consists of cefepime, a cephalosporin antibacterial, and enmetazobactam, a beta-lactamase inhibitor. The approval was based on data from a double-blind, noninferiority phase 3 trial (ClinicalTrials.gov Identifier: NCT03687255) that evaluated the efficacy and safety of cefepime/enmetazobactam in 1041 adults with cUTI, including pyelonephritis.

Study participants were randomly assigned 1:1 to receive cefepime 2g/enmetazobactam 500mg (n=345) or piperacillin 4g/tazobactam 500mg (n=333) every 8 hours for 7 days, or up to 14 days for patients with concurrent bacteremia. 

The primary efficacy endpoint was composite response defined as clinical cure (complete resolution of the baseline signs/symptoms of cUTI or pyelonephritis that were present at screening) and microbiological eradication (Gram negative pathogens reduced to <10³ colony-forming units/mL in urine culture and a negative blood culture for a Gram negative pathogen that was identified as a uropathogen) at the test-of-cure (TOC) visit.

Results showed that 79.1% (273/345) of patients treated with cefepime/enmetazobactam achieved composite response compared with 58.9% (196/333) of the piperacillin/tazobactam group (adjusted stratified difference, 21.2% [95% CI, 14.3-27.9]). Among patients with bacteremia at baseline, 71% (27/38) of patients treated with cefepime/enmetazobactam achieved composite response compared with 50% (14/28) of the piperacillin/tazobactam group.

Among study participants with extended spectrum beta-lactamase (ESBL)-producing bacteria at baseline, composite response was observed at TOC in 74% (56/76) of patients treated with cefepime/enmetazobactam and 52% (34/66) of those treated with  piperacillin/tazobactam.

The most common adverse reactions reported with cefepime/enmetazobactam were increased transaminases, increased bilirubin, headache, and phlebitis/infusion site reactions.

Exblifep is supplied in cartons of 10 single-dose vials; each vial contains 2 grams of cefepime and 0.5 grams of enmetazobactam as a powder for reconstitution. Following reconstitution and further dilution, treatment is administered via intravenous infusion.