The Antimicrobial Drugs Advisory Committee of the Food and Drug Administration has voted to recommend plazomicin, a new aminoglycoside, for systemic use in the treatment of complicated urinary tract infections (cUTI) but rejected it for treatment of blood stream infections (BSIs) that are caused by multidrug resistant (MDR) Enterobacteriaceae.
Advisers voted unanimously to recommend plazomicin for cUTI, but rejected the drug for BSIs in an 11-4 no vote, based on the results of two phase 3 clinical trials: EPIC and CARE.
“Today’s meeting brought the committee face to face with the crisis of multidrug resistant bacteria,” he said. “Results of the 009 [EPIC] study, in my mind, clearly showed plazomicin met the noninferiority endpoints.”
EPIC study
EPIC was a phase 3 clinical trial to assess the noninferiority of plazomicin to meropenem in patients with cUTI and/or acute pyelonephritis (AP). Many patients with drug resistant infections have limited treatment options, so plazomicin was reviewed under the Limited Population Antibacterial Drug pathway.
Patients in the study were stratified by geographical region and infection type – cUTI or acute pyelonephritis (AP). In total, 609 patients were randomized in the intent-to-treat (ITT) group with 306 and 303 receiving plazomicin or meropenem, respectively. Using the coprimary efficacy endpoints of microbiological eradication and clinical cure, a measure known as composite cure was developed to assess efficacy at Day 5 and the test of cure (TOC) visit in the microbiological modified intent-to-treat (mMITT) population. The mMITT group consisted of all patients who had received any dose of study drug and had at least one qualified baseline pathogen with 105 or more colony-forming units/mL that was susceptible to both meropenem and plazomicin.Plazomicin was noninferior to meropenem with a margin of 15%. At day 5, the composite cure rate was 88% in the plazomicin group, compared with 91.4% in the meropenem group. Similar results were seen at the test of cure visit, with composite cure rates of 81.7% and 70.1% in the plazomicin and meropenem groups, respectively.