FDA Approves Therapy for Hospital-Based Bacterial Pneumonias

Shionogi announced today that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application for cefiderocol for the treatment with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by the following susceptible Gram-negative microorganisms in patients 18 years of age or older.

“Antimicrobial resistance is a major global health concern, and there is a clear need for new treatments such as FETROJA (cefiderocol) to give clinicians more options to fight life-threatening infections caused by Gram-negative pathogens,” said Akira Kato, PhD, president and CEO at Shionogi Inc. “This milestone represents Shionogi’s long-standing and unwavering commitment to constantly fight evolving infectious diseases in an era realizing significant unmet needs.”

Cefiderocol is currently approved for patients 18 years of age or older for the treatment of complicated urinary tract infections, including pyelonephritis, caused by Gram-negative pathogens. It is the first approved antibiotic that functions as a siderophore and has a novel mechanism for penetrating the outer cell membrane of Gram-negative pathogens including carbapenem-resistant strains.

This expanded indication is based on the results of the phase 3 APEKS-NP study, which showed cefiderocol met the primary endpoint of non-inferiority compared to high-dose extended-infusion meropenem in all-cause mortality 14 days after initiation of study drug in the treatment of patients with HABP, VABP and healthcare-associated bacterial pneumonia (HCABP).

Cefiderocol is a cephalosporin antibiotic with a novel mechanism for penetrating the outer cell membrane of Gram-negative pathogens by acting as a siderophore. In addition to entering cells by passive diffusion through porin channels, cefiderocol binds to ferric iron and is actively transported into bacterial cells through the outer membrane via the bacterial iron transporters, which function to incorporate this essential nutrient for bacteria. These mechanisms allow cefiderocol to achieve high concentrations in the periplasmic space where it can bind to penicillin-binding proteins and inhibit cell wall synthesis in the bacterial cells.

“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,” said APEKS-NP principal investigator Richard G. Wunderink, MD, Northwestern University Feinberg School of Medicine. “The results from the APEKS-NP study show that cefiderocol is a much-needed additional option for the treatment of patients with HABP and VABP due to multidrug-resistant Gram-negative bacteria.”