Shionogi can sell antibiotic Fetcroja in EU for infections

Shionogis’ Fetcroja (cefiderocol) has received European Commission (EC) marketing authorisation for the treatment of infections due to aerobic Gram-negative bacteria in adults with limited treatment options.

OSAKA, Japan & AMSTERDAM–(BUSINESS WIRE)–FOR EUROPEAN MEDICAL AND PHARMA TRADE MEDIA ONLY

Shionogi & Co., Ltd. (Head Office: Osaka, Japan; President & CEO: Isao Teshirogi, Ph.D.) and its European subsidiary, Shionogi B.V. (hereafter “Shionogi”) today announces that the European Commission (EC) has granted a marketing authorisation for cefiderocol, a new antibiotic for the treatment of infections due to aerobic Gram-negative bacteria in adults (18 years or older) with limited treatment options.

Cefiderocol has extensive in vitro activity against a broad spectrum of aerobic Gram-negative pathogens.

The EC approval of cefiderocol was based on the non-clinical data package, including the PK/PD data package. Data from multinational surveillance studies for cefiderocol demonstrated potent in vitro activity against a broad spectrum of aerobic Gram-negative pathogens including all three WHO critical priority pathogens: carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales, as well as Stenotrophomonas maltophilia. Cefiderocol also demonstrated in vitro activity against certain bacteria that contain very problematic resistant enzymes such as ESBLs, AmpC, serine- and metallo-carbapenemases.

“Antimicrobial resistance is a growing global health threat that is only set to get worse if no action is taken, so it is very welcome news that this new and effective antibiotic has now been approved in Europe,” said Prof. Peter Hawkey, Institute of Microbiology and Infection College of Medical and Dental Sciences, University of Birmingham. “Cefiderocol is active against all the critical pathogens that are most concerning to the World Health Organization so will be a much-needed option for clinicians treating some of the most severe Gram-negative infections.”

In an update, Mark D Hill, Senior Vice President Shionogi & Co. told Pharmaceutical Daily that, in the EU, Shionogi is building quickly its commercial and supply infrastructure to ensure Fetcroja is available to all patients who need it as soon as possible, and expect first commercial launches within the coming weeks.

Cefiderocol

Cefiderocol is the world’s first siderophore cephalosporin antibiotic with a novel mechanism of entry through the outer membrane of Gram-negative pathogens by using the bacteria’s own iron uptake system to gain cell entry, acting like a Trojan horse. 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 higher concentrations in the periplasmic space where it can bind to penicillin-binding proteins and inhibit cell wall synthesis in the bacterial cells.

Carbapenem resistance (CR) in Gram-negative bacteria is due to three main mechanisms:

• Beta-lactamases which cause enzymatic breakdown of beta-lactams
• Changes in porin channels (through mutations and decrease in number) through which beta-lactams and other antibiotics diffuse into cells,
• Overexpression of efflux pumps which occurs post-exposure and pumps antibiotics out of cells

As a result of its novel structure and mechanism of cell uptake, cefiderocol can overcome these three major mechanisms of CR.

“This approval represents another significant milestone in 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,” said Takuko Sawada, Director of the Board, Executive Vice President. “Cefiderocol’s novel mechanism of cell entry is like a Trojan horse; it exploits the bacteria’s own iron uptake transporters to effectively enter the bacterial cell, which allows it to overcome the three major mechanisms of carbapenem-resistance in Gram-negative bacteria.”

As a result of COVID-19 some ventilated patients with viral pneumonia may develop secondary carbapenem-resistant Gram-negative bacterial infections. Similar to nosocomial pneumonia patients with carbapenem-resistant Gram-negative infections, Cefiderocol may be a considered as a treatment option.