Shionogi has announced positive results from the phase 3 APEKS-NP trial of cefiderocol (S-649266) for the treatment of nosocomial pneumonia.
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.
APEKS-NP was a multicenter, double-blind, parallel-group trial that compared the all-cause mortality of cefiderocol at Day 14 to high-dose meropenem in 300 adults with nosocomial pneumonia. Patients were randomized 1:1 to receive either cefiderocol or meropenem administered 2g IV every 8 hours for 7 to 14 days in combination with linezolid 600mg IV every 12 hours for at least 5 days. The primary end point was all-cause mortality at Day 14; key secondary end points included clinical and microbiological outcomes at test of cure (TOC), defined as 7 days after the end of treatment, and all-cause mortality at Day 28.
Results demonstrated cefiderocol to be noninferior to meropenem; all-cause mortality at Day 14 in the modified intent-to-treat population was 12.4% for cefiderocol (n=18/145) compared with 11.6% for meropenem (n=17/146) (difference: 0.8, 95% CI: -6.6; 8.2). In addition, the clinical outcome of clinical cure at TOC was observed in 64.8% of cefiderocol-treated patients and 66.7% of meropenem-treated patients (difference: -2.0, 95% CI: -12.5; 8.5), while the percentage of patients with microbiological eradication at TOC was 47.6% and 48%, respectively (difference: -1.4, 95% CI: -13.5; 10.7). At Day 28, all-cause mortality in the cefiderocol arm was 21.0% compared with 20.5% for the meropenem group (difference: 0.5, 95% CI: -8.7; 9.8).
With regard to safety, the incidence of treatment-emergent adverse events was similar between cefiderocol, 87.8%, and meropenem, 86% (difference: 1.8, 95% CI: -5.8; 9.5).
Full clinical study findings will be presented at IDWeek in Washington, DC.
“Carbapenem resistance is a growing problem in the US and around the world, with increasing infections due to strains that are resistant to most or all currently available antibiotics,” said Dr Tsutae “Den” Nagata, Chief Medical Officer, Shionogi. “These phase 3 APEKS-NP data, combined with data from our phase 2 APEKS-cUTI trial in complicated urinary tract infection, underscore the potential of cefiderocol to help solve an unmet medical need for patients battling life-threatening infections caused by deadly, hard-to-treat Gram-negative pathogens.”
Shionogi submitted a New Drug Application (NDA) for cefiderocol to the Food and Drug Administration (FDA) in December 2018. Moreover, the FDA previously granted Qualified Infectious Disease Product (QIDP) designation to cefiderocol with the assigned action date of November 14, 2019 under the Prescription Drug User-Fee Act (PDUFA).
For more information visit shionogi.com.