One year after Fetroja approval, Shionogi expands label to include difficult-to-treat pneumonia
A year after snagging approval in complicated urinary tract infections, Shionogi’s antibiotic Fetroja has added another indication to its label: hospital-acquired and ventilator-associated bacterial pneumonia.
The FDA OK was based on Phase III data which showed the drug — chemically known as cefiderocol — was non-inferior to high-dose meropenem in all-cause mortality (ACM) after two weeks. According to the Japanese biotech, 12.4% of modified intent-to-treat patients on Fetroja died after 14 days, compared to 12.2% of patients on meropenem.
Participants in the trial, dubbed APEKS-NP, were given 2 grams of either Fetroja or meropenem over a 3-hour period every 8 hours for 14 days. At Day 28, ACM was at 22.1% for Fetroja patients, and 21.1% for high-dose meropenem patients. The rate of treatment-emergent adverse events was slightly higher for those on Fetroja versus meropenem: 87.8% and 86.0% respectively.
“Antimicrobial resistance is a major global health concern, and there is a clear need for new treatments such as FETROJA to give clinicians more options to fight life-threatening infections caused by Gram-negative pathogens,” Shionogi CEO Akira Kato said in a statement.
Cefiderocol was approved last November for cUTIs. It’s designed to bind to ferric iron and enter the outer membrane of bacterial cells via the iron transporters.
In a study with 448 cUTI patients, 72.6% were clear of bacteria and symptoms after 7 days, compared to 54.6% of patients in the control arm, according to the FDA. But the drug came with a grim warning: Some patients on Fetroja had a higher mortality rate compared to those on the best available therapy. All-cause mortality was 24.8% in nosocomial pneumonia, bloodstream infection and sepsis patients treated with Fetroja after 28 days, versus 18.4% on other therapies, according to the company. The cause of the increased mortality is unknown, according to the drug’s warning label.
Nosocomial pneumonia is particularly difficult to treat. Last May, it tripped up Swiss biotech Polyphor, which halted enrollment in its pivotal Phase III trial for murepavadin after investigators noticed high rates of acute kidney injury.
“Nosocomial pneumonia is one of the most common hospital-acquired infections and a rising number are caused by difficult-to-treat, multidrug-resistant pathogens, which can be a deadly threat for patients,” Richard Wunderink, APEKS principal investigator and Northwestern University Feinberg School of Medicine professor, said in a statement.
In January, the WHO noted a lack of new antibiotics in the making, as drug developers are attracted to other fields. “Never has the threat of antimicrobial resistance been more immediate and the need for solutions more urgent,” Tedros Adhanom Ghebreyesus, WHO director-general, said in a statement.