The U.S. Food and Drug Administration (FDA) approved Shionogi’s Fetroja as a treatment for adult patients with complicated urinary tract infections caused by a number of Gram-negative microorganisms.
The approval came only a few days after the U.S. Centers for Disease Control and Prevention issued a report that antibiotic-resistant infections have grown significantly in the United States over the past six years. The CDC said more than 2.8 million antibiotic-resistant infections annually occurred in the U.S., leading to the deaths of more than 35,000 people. Of those deaths, Clostridioides difficile (C. diff) infections resulted in nearly half, with 12,800 deaths.
John Farley, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, said the growing threat antimicrobial-resistant infections is a key challenge for the regulatory agency. The approval of Fetroja “represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections,” Farley said in a statement.
The approval of Fetroja marks the first antibiotic to function as siderophore, a molecule that transports iron into microorganisms. Once inside the bacteria, Fetroja is stable against all known classes of beta-lactamases. Fetroja addresses many of the resistance mechanisms that bacteria employ against antibiotics, the company said.
Fetroja was approved under Fast Track Designation and Priority Review and is expected to be commercially available in early 2020. Isao Teshirogi, president and chief executive officer of Japan-based Shionogi, said the approval of Fetroja will fill an important unmet medical need due to its “unique method” of penetrating the cell wall of Gram-negative bacteria. Those Gram-negative microorganisms specifically indicated for Fetroja’s use by the FDA include Escherichia coli, Klebsiella pneumonia, Proteus mirabilis, Pseudomonas aeruginosa and Enterobacter cloacae complex. Teshirogi also pointed to the drug’s ability to “overcome” many of the resistance mechanisms that bacteria employ against antibiotics.
“Today’s approval represents Shionogi’s ongoing commitment to develop medicines that help fight these life-threatening infections in patients for whom limited or no alternative treatment options exist,” Teshirogi said in a statement.
Approval of the drug is based on data from the pivotal APEKS-cUTI study that evaluated Fetroja (cefiderocol) against imipenem/cilastatin (IPM/CS) in patients with cUTI. Results from that study showed the response rates for the composite endpoint of microbiological eradication and clinical response at the test of cure were significantly higher in the Fetroja arm compared to the IPM/CS arm. In the study, 72.6% of Fetroja patients met the primary endpoint versus 54.6% in the IPM/CS arm at test of cure. The adjusted difference between the groups was 18.58%, the company added. Clinical response rates at the test of cure visit were similar between both Fetroja and IPM/CS. That data was strong enough for an advisory committee to vote 14-2 last month in favor of approval.
The approval for Fetroja does come with a black box warning. The label includes a warning regarding the higher all-cause mortality rate observed in Fetroja-treated patients compared to those treated with other antibiotics in a trial in critically ill patients with multidrug-resistant Gram-negative bacterial infections. The FDA said it has not been established what has caused the increase in mortality rate. The higher all-cause mortality rate was observed in patients treated for hospital-acquired/ventilator-associated pneumonia, bloodstream infections, or sepsis, the FDA said.
The most common were diarrhea, infusion site reactions, constipation, rash, candidiasis, cough, elevations in liver tests, headache, hypokalemia, nausea and vomiting.
