ESCMID Global 2025: Shionogi presents real-world data demonstrating better clinical outcomes when Fetcroja^® / Fetroja^® (cefiderocol) is used as empiric or documented therapy as compared to salvage therapy for the treatment of Gram-negative bacterial infections

OSAKA, Japan, April 8, 2025 – Shionogi & Co., Ltd. (Head Office: Osaka, Japan; President & CEO: Isao Teshirogi, Ph.D.; hereafter “Shionogi”) presents new European data from its largest real-world evidence study of Fetroja^®/Fetcroja^® (cefiderocol), an innovative siderophore cephalosporin at the 35th Congress of the European Society of Clinical Microbiology and Infectious Diseases in Vienna on 11th-15th April 2025.

Please see below under About Cefiderocol the Full indications, and Important Safety Information of Fetroja.

The PROVE (Retrospective Cefiderocol Chart Review) study is a five-year international, retrospective, observational medical chart review study, conducted between November 2020 and July 2024 designed to describe the efficacy and safety of real-world cefiderocol use in adult patients with serious Gram-negative (GN) bacterial infections.¹

Analysis of the European cohort found a higher clinical cure rate trend among patients who received cefiderocol for a documented infection (67.4%) or as empiric therapy (64.6%) as compared to those who received it as salvage therapy (58.2%).³

Professor Oliver Cornely, Director of Translational Research, University of Cologne, said: “These data suggest a trend towards worse clinical outcomes when the use of cefiderocol to treat Gram-negative bacterial infections is reserved as a last line treatment option compared with those who received the treatment earlier. This trend may offer clinicians new evidence to justify the early and effective use of cefiderocol in patients with suspected resistant infections.”

The study analysed data from 567 patients hospitalised with confirmed GN bacterial infections, who were treated with cefiderocol for the first time for ≥72 hours across Spain, France, Italy, Germany and the United Kingdom.¹ Carbapenem resistance rate was >70% among patients enrolled in the study.¹ 55.9% of patients were critically ill in the intensive care unit and 41.3% were receiving organ support at the point of cefiderocol initiation.¹

Respiratory tract infection (RTI) was the most frequent infection site, reported in over 50% of patients (299), followed by urinary tract infection in over 12% of patients (73).¹

Patients in the study receiving cefiderocol across all pathogens achieved an overall clinical cure rate of 65.3%.¹ The most frequent pathogens observed were Pseudomonas aeruginosa (41.3%), Acinetobacter baumannii (15.0%) and Enterobacterales (14.6%)¹, which are identified as priority pathogens by the World Health Organisation.² A clinical cure rate of 73.1% was observed among patients with a Pseudomonas aeruginosa infection.¹

Takuko Sawada, Board Director and Vice Chair, Shionogi & Co., Ltd., said: “Antimicrobial resistance is one of the most pressing global health challenges of this century, resulting in the deaths of millions of people around the world each year. In order to support better patient outcomes, it is imperative that clinicians have access to the innovative treatments they need for appropriate use with the right patient at the right time. We remain committed to the research and development of essential medicines that will help tackle the growing threat of drug-resistant infection.”

Shionogi & Co., Ltd. is a 146-year-old global, research-driven pharmaceutical company headquartered in Osaka, Japan, that is dedicated to bringing benefits to patients based on its corporate philosophy of “supplying the best possible medicine to protect the health and wellbeing of the patients we serve.” The company currently markets products in several therapeutic areas including anti-infectives, pain, CNS disorders, cardiovascular diseases and gastroenterology. Shionogi’s research and development currently target two therapeutic areas: infectious diseases and pain/CNS disorders.

For more information on Shionogi & Co., Ltd., please visit https://www.shionogi.com/global/en. 

Shionogi has a strong heritage in the field of anti-infectives and has been developing antimicrobial therapies for more than 60 years. Shionogi is proud to be one of the few large pharmaceutical companies that continues to focus on R&D in anti-infectives. 

In Europe, cefiderocol is commercially available under the brand name Fetcroja^® for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.⁴ In the US, cefiderocol is commercially available under the brand name Fetroja^® and is indicated in patients 18 years of age or older for the treatment of hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia and complicated urinary tract infections caused by certain susceptible Gram-negative microorganisms.⁵ In Japan, cefiderocol is commercially available under the brand name Fetroja^® and received manufacturing and marketing approval from the Ministry of Health, Labour and Welfare for various infections caused by strains resistant to carbapenem antibiotics among sensitive strains of Escherichia coli, Citrobacter species, Klebsiella pneumoniae, Enterobacter species, Serratia marcescens, Proteus species, Morganella morganii, Pseudomonas aeruginosa, Burkholderia species, Stenotrophomonas maltophilia, and Acinetobacter species.⁶

Fetroja^® (cefiderocol) is indicated in patients 18 years of age or older for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Enterobacter cloacae complex.

Fetroja is indicated in patients 18 years of age or older for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by the following susceptible Gram-negative microorganisms: Acinetobacter baumannii complex, Escherichia coli, Enterobacter cloacae complex, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Fetroja and other antibacterial drugs, Fetroja should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Fetroja is contraindicated in patients with a known history of severe hypersensitivity to cefiderocol or other beta-lactam antibacterial drugs, or any other component of Fetroja.

An increase in 28-day all-cause mortality was observed in Fetroja-treated nosocomial pneumonia, bloodstream infections, or sepsis patients compared to those treated with best available therapy (BAT) in a clinical study (NCT02714595). Most BAT regimens contained colistin. All-cause mortality remained higher in patients treated with Fetroja than in patients treated with BAT through Day 49.

Generally, deaths were in patients with infections caused by Gram-negative organisms, including non-fermenters such as Acinetobacter baumannii complex, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa, and were the result of worsening or complications of infection, or underlying comorbidities. The cause of the increase in mortality has not been established. Closely monitor the clinical response to therapy in patients with cUTI and HABP/VABP.

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. Hypersensitivity was observed with Fetroja. Before Fetroja is instituted, inquire about previous hypersensitivity to cephalosporins, penicillins, or other beta-lactam drugs. If an allergic reaction occurs, discontinue Fetroja.

CDAD has been reported with nearly all systemic antibacterial agents, including Fetroja. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterial drugs not directed against C. difficile may need to be discontinued.

Cephalosporins, including Fetroja, have been implicated in triggering CNS adverse reactions such as seizures. Encephalopathy, coma, asterixis, and neuromuscular excitability have been reported with cephalosporins, particularly in patients with a history of epilepsy and/or when recommended dosages of cephalosporins were exceeded due to renal impairment. Adjust Fetroja dosing based on creatinine clearance. If focal tremors or seizures occur, evaluate patients to determine whether Fetroja should be discontinued.

Prescribing Fetroja in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

The most common adverse reactions occurring in ≥2% of patients receiving Fetroja in the cUTI trial were: diarrhea (4%), infusion site reactions (4%), constipation (3%), rash (3%), candidiasis (2%), cough (2%), elevations in liver tests (2%), headache (2%), hypokalemia (2%), nausea (2%), and vomiting (2%). The most common adverse reactions occurring in ≥4% of patients receiving Fetroja in the HABP/VABP trial were: elevations in liver tests (16%), hypokalemia (11%), diarrhea (9%), hypomagnesemia (5%), and atrial fibrillation (5%).

Please click here for Full U.S. Prescribing Information for Fetroja® (cefiderocol).

This announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions such as general industry and market conditions, and changes of interest rate and currency exchange rate. These risks and uncertainties particularly apply with respect to product-related forward-looking statements. Product risks and uncertainties include, but are not limited to, completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations. Also for existing products, there are manufacturing and marketing risks, which include, but are not limited to, inability to build production capacity to meet demand, lack of availability of raw materials and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise.

For Further Information, Contact:

SHIONOGI Website Inquiry Form: https://www.shionogi.com/global/en/contact.html

Shionogi Europe Press Office: pressoffice@shionogi.eu

U.S. Media Contact: ShionogiCommunications@shionogi.com

1. Asensio Martin JM et al. Cefiderocol treatment in patients with Gram-negative bacterial infections: European results of the global retrospective observational PROVE study. Abstract. ESCMID 2025.

 

2. WHO Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance.

 

3. Asensio Martin JM et al. Cefiderocol treatment in patients with Gram-negative bacterial infections: European results of the global retrospective observational PROVE study. Poster 2542. ESCMID 2025.

 

4. Fetroja^® Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/fetcroja-epar-product-information_en.pdf . Accessed: March 2024.

 

5. Fetroja^® Prescribing information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209445s000lbl.pdf. Accessed: March 2024.

 

6. Press release on November 30, 2023. Regarding the Acquisition of Manufacturing and Marketing Approval for the New Siderophore Cephalosporin Antibiotic Fetroja^® (cefiderocol) Intravenous Infusion 1g vial in Japan.