Shionogi has announced that cefiderocol (S-649266), a novel siderophore cephalosporin in late-stage development, met the FDA pre-specified primary endpoint for non-inferiority vs imipenem/cilastatin (IPM/CS) in patients with serious complicated urinary tract infection (cUTI) with Gram-negative bacteria. Cefiderocol was superior to IPM/CS at test of cure (TOC).
The study APEKs-cUTI enrolled 452 patients with cUTI. The median duration of treatment was nine days for both cefiderocol and IPM/CS for all populations. Cefiderocol met the FDA primary efficacy endpoint of composite of clinical cure and microbiologic eradication at test of cure (TOC) in 72.6% of patients (n=252) which was superior to IPM/CS at 54.6% (n=119), a weighted difference of 18.58% (95% CI: 8.23, 28.92).
"We are very excited about the results of this trial. Unlike most studies, this cUTI study was designed to include patients that are more difficult to treat. The data clearly demonstrate that cefiderocol will be an important option for serious Gram-negative infections," said Dr. Tsutae Den Nagata, chief medical officer.
Cefiderocol was well tolerated in the study, with 40% of patients experiencing an adverse event in the cefiderocol arm vs 50% of patients in the IPM/CS arm. Serious adverse events (SAEs) occurred in 14 patients (4.7%) who received cefiderocol and 12 patients (8.1%) who received IPM/CS. Shionogi plans to submit an NDA for cefiderocol to the FDA in 2017. The data from the APEKs-cUTI clinical study are planned to be presented in early 2017.
APEKs-cUTI was an international multicenter, double-blind, randomized, non-inferiority trial designed to evaluate the efficacy, safety, and tolerability of cefiderocol vs IPM/CS in hospitalized adult patients with cUTI, with or without pyelonephritis, at TOC (approximately seven days following the end of treatment). The study permitted enrollment of immunocompromised patients, including renal transplant, and limited acute uncomplicated pyelonephritis to less than 30%. Switch to oral therapy was not permitted. Patients with Gram-negative pathogens were randomized on a 2:1 basis to receive cefiderocol (2 grams) administered intravenously every eight hours, or high-dose IPM/CS (1/1 gram) administered intravenously every eight hours, for seven to 14 days in hospital. Of the 452 patients randomized, 448 were treated and 371 met the definition of the micro-ITT population and were assessed for efficacy. All treated subjects were assessed for safety.