FDA News

FDA approves Fetroja for treatment of complicated UTIs

Shionogi won FDA approval for Fetroja for the treatment of complicated UTIs, or cUTIs, in adults with limited or no alternative treatment options.

Fetroja (cefiderocol) is a siderophore cephalosporin with a novel mechanism for penetrating gram-negative pathogens, including multidrug-resistant strains.

“Fetroja will fill a very important unmet medical need because of its unique method of penetrating the cell wall of gram-negative bacteria and its ability to overcome many of the resistance mechanisms that bacteria employ against antibiotics,” Shionogi President and CEO Isao Teshirogi, PhD, said in a news release.

According to the release, the approval was based on data from the APEKS-cUTI study, which showed a significantly higher composite endpoint of microbiological eradication and clinical response at test of cure in the cefiderocol group compared with participants who received imipenem/cilastatin. Overall, 72.6% of patients in the cefiderocol group met the primary endpoint vs. 54.6% in the imipenem/cilastatin group.

“In the pivotal study, cefiderocol achieved a higher response rate compared to imipenem/cilastatin,” George H. Karam, MD, MACP, Paula Garvey Manship Chair of Medicine at the Louisiana State University School of Medicine, said in the release. “With [the] approval of cefiderocol, the infectious disease community now has a new type of antibiotic with a unique mechanism of cell entry to add to their toolkit to assist in the complexity of treating highly resistant pathogens that are occurring with increasing frequency in life-threatening infections.”

The approval comes with several related warnings.

In a study called CREDIBLE-CR, researchers observed an increase in all-cause mortality in critically patients with carbapenem-resistant gram-negative bacterial infections treated with cefiderocol compared with the best available therapy. The increase was seen in patients treated for nosocomial pneumonia, bloodstream infections or sepsis, in which the safety and efficacy of cefiderocol has not been established, Shionogi said.

“Generally, deaths were in patients with infections caused by gram-negative organisms, including nonfermenters such as Acinetobacter baumannii, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa, and were the result of worsening or complications of infection, or underlying comorbidities,” the company explained. “The cause of the increase in mortality has not been established.”

According to the company, hypersensitivity, which is more likely to occur in individuals with a history of beta-lactam hypersensitivity and/or a history of sensitivity to multiple allergens, also was observed in clinical trials for cefiderocol.

Like many antibacterial agents, Clostridioides difficile-associated diarrhea has been reported in patients taking cefiderocol, Shionogi said. It said cefiderocol also may increase the risk for development of drug-resistant bacteria when given “in the absence of a proven or strongly suspected bacterial infection.” – by Caitlyn Stulpin

Disclosures: Teshirogi is employed by Shionogi. Infectious Disease News could not confirm the relevant financial disclosures for Karam.

Shionogi won FDA approval for Fetroja for the treatment of complicated UTIs, or cUTIs, in adults with limited or no alternative treatment options.

Fetroja (cefiderocol) is a siderophore cephalosporin with a novel mechanism for penetrating gram-negative pathogens, including multidrug-resistant strains.

“Fetroja will fill a very important unmet medical need because of its unique method of penetrating the cell wall of gram-negative bacteria and its ability to overcome many of the resistance mechanisms that bacteria employ against antibiotics,” Shionogi President and CEO Isao Teshirogi, PhD, said in a news release.

According to the release, the approval was based on data from the APEKS-cUTI study, which showed a significantly higher composite endpoint of microbiological eradication and clinical response at test of cure in the cefiderocol group compared with participants who received imipenem/cilastatin. Overall, 72.6% of patients in the cefiderocol group met the primary endpoint vs. 54.6% in the imipenem/cilastatin group.

“In the pivotal study, cefiderocol achieved a higher response rate compared to imipenem/cilastatin,” George H. Karam, MD, MACP, Paula Garvey Manship Chair of Medicine at the Louisiana State University School of Medicine, said in the release. “With [the] approval of cefiderocol, the infectious disease community now has a new type of antibiotic with a unique mechanism of cell entry to add to their toolkit to assist in the complexity of treating highly resistant pathogens that are occurring with increasing frequency in life-threatening infections.”

The approval comes with several related warnings.

In a study called CREDIBLE-CR, researchers observed an increase in all-cause mortality in critically patients with carbapenem-resistant gram-negative bacterial infections treated with cefiderocol compared with the best available therapy. The increase was seen in patients treated for nosocomial pneumonia, bloodstream infections or sepsis, in which the safety and efficacy of cefiderocol has not been established, Shionogi said.

“Generally, deaths were in patients with infections caused by gram-negative organisms, including nonfermenters such as Acinetobacter baumannii, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa, and were the result of worsening or complications of infection, or underlying comorbidities,” the company explained. “The cause of the increase in mortality has not been established.”

According to the company, hypersensitivity, which is more likely to occur in individuals with a history of beta-lactam hypersensitivity and/or a history of sensitivity to multiple allergens, also was observed in clinical trials for cefiderocol.

Like many antibacterial agents, Clostridioides difficile-associated diarrhea has been reported in patients taking cefiderocol, Shionogi said. It said cefiderocol also may increase the risk for development of drug-resistant bacteria when given “in the absence of a proven or strongly suspected bacterial infection.” – by Caitlyn Stulpin

Disclosures: Teshirogi is employed by Shionogi. Infectious Disease News could not confirm the relevant financial disclosures for Karam.