The world's first iron carrier cephalosporin drug is approved in the EU

The Japanese pharmaceutical company Shionogi recently announced that the European Commission (EC) has approved the new antibacterial drug Fetcroja (cefiderocol, cefadil) for use in adult patients (18 years and older) with limited treatment options. Infections caused by Gram-negative bacteria.

It is worth mentioning that cefiderocol is the world's first iron carrier cephalosporin that uses the bacteria's own iron absorption system to enter bacterial cells in a manner similar to the "Trojan horse". Cefiderocol has broad antibacterial activity in vitro against a broad spectrum of aerobic Gram-negative pathogens.

Data from cefiderocol's multinational surveillance study shows that cefiderocol is in vitro against a broad spectrum of aerobic Gram-negative pathogens (including all three key priority pathogens listed by the World Health Organization: carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, refractory carbapenem-resistant Enterobacteriaceae) and Stenotrophomonas maltophilia have strong inhibitory effects. In addition, cefiderocol is also capable of producing a variety of drug-resistant enzymes (such as extended-spectrum β-lactamase [ESBL], AmpC β lactamase [AmpC], serine carbapenemase and metal carbapenemase). These bacteria have strong antibacterial activity in vitro. The approval is based on non-clinical data and PK / PD data packages (including in vitro data) and clinical data support for three key clinical studies (APEKS-cUTI, APEKS-NP, CREDIBLE-CR) submitted by Yoshino. Data from these 3 studies demonstrate the efficacy of cefiderocol in patients with the following infection types: complex urinary tract infection (cUTI), hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and sepsis (including complex intra-abdominal infections [ cIAI]), skin and skin structure infection (SSSI), bacteremia (some patients do not have a confirmed primary infection). One of the studies included patients with Gram-negative infections caused by multi-drug resistant pathogens (including carbapenem-resistant bacteria, etc.) on the WHO priority list.

Cefiderocol is the first approved antibiotic with iron carrier function, which can overcome many of the resistance mechanisms of Gram-negative bacteria to antibiotics, by inhibiting the formation of peptidoglycan (an important part of the bacterial cell wall). In addition, cefiderocol is the only available antibiotic with strong in vitro activity against all gram-negative bacteria with the highest priority determined by the World Health Organization (WHO).

In the United States, cefiderocol (brand name: Fetroja) was approved by the FDA on November 14, 2019 for the treatment of adult patients aged 18 years and over with limited or no treatment options. The treatment is caused by the following susceptible Gram-negative microorganisms Complex urinary tract infections (cUTI, including pyelonephritis): E. coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Enterobacter cloacae complex. Prior to this, cefiderocol has been awarded the Qualified Infectious Disease Product (QIDP) Qualification, Fast Track Qualification, and Priority Review by the FDA. The active pharmaceutical ingredient of Fetroja / Fetcroja is cefiderocol, which is a new type of iron carrier cephalosporin, which has a unique mechanism of penetrating the cell membrane of gram-negative bacteria (including multi-drug resistant bacteria) and has the ability to overcome carba The unique ability of three main mechanisms of ene resistance (altered porin channels, inactivation of β-lactamase, and excessive production of efflux pumps). Cefiderocol binds to ferric iron and is actively transported into bacterial cells through the outer membrane of the cell membrane through the bacterial iron transport protein. This Trojan horse strategy allows cefiderocol to reach higher concentrations in the bacterial cell periplasm, binds to penicillin-binding proteins in the periplasmic space and inhibits bacterial cell wall synthesis.

In vitro studies have shown that cefiderocol has strong activity against all Gram-negative bacteria with the highest priority identified by the World Health Organization (WHO), including key carbapenem-resistant Gram-negative non-fermentative Acinetobacter baumannii, aeruginosa Pseudomonas, refractory carbapenem-resistant Enterobacteriaceae. Cefiderocol is developed for use in diseases where the mortality rate is high and there are serious unmet medical needs.

Antibiotic resistance (AMR) is a health burden that needs to be addressed urgently. In the United States and Europe alone, 56,000 people die of antibiotic-resistant infections each year. If no measures are taken, 10 million people will die each year from antibiotic-resistant infections, and by 2050, the global economic burden will be $ 100 trillion.

Based on the unique way of penetrating the cell wall of Gram-negative bacteria and the ability to overcome the multiple resistance mechanisms of bacteria to antibiotics, cefiderocol will help fill a very important unmet medical need after it is launched.