OSAKA, Japan & FLORHAM PARK, N.J.–(BUSINESS WIRE) September 28, 2020 –Shionogi & Co., Ltd. (hereafter “Shionogi”) today announces that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for Fetroja® (cefiderocol) for the treatment of patients 18 years of age or older with 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.
Shionogi today announces that the U.S. FDA has approved a sNDA for Fetroja® (cefiderocol) for the treatment of patients 18 years of age or older with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.
This expanded indication is based on the results of the Phase III APEKS-NP study, which showed Fetroja 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).
“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, M.D., 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.”
Fetroja 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. See the full indication below.
APEKS-NP (Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Stenotrophomonas maltophilia in Nosocomial Pneumonia) was a multinational, multicenter, double-blind, randomized, trial designed to evaluate the efficacy and safety of Fetroja for the treatment of nosocomial pneumonia including HABP, VABP, and HCABP caused by Gram-negative pathogens. Patients were randomized on a 1:1 basis to receive Fetroja administered by intravenous infusion of two grams over a three-hour period every eight hours or high-dose extended-infusion meropenem administered as two grams over a three-hour period every eight hours, for seven to 14 days in the hospital. Linezolid was additionally administered for at least five days in both arms to provide coverage for methicillin-resistant Staphylococcus aureus (MRSA), and for Gram-positive bacteria in the Fetroja group. Safety was investigated up to 28 days after the end of treatment unless there was an ongoing adverse event(s) which were followed up until their resolution.
The study found that Fetroja:
- Met the primary endpoint of non-inferiority to high-dose meropenem, infused over three hours. At Day 14, all-cause mortality (ACM) in the modified intent-to-treat population was 12.4% for Fetroja (18/145) and 12.2% for high-dose meropenem (18/147), respectively (difference: 0.2, 95% CI: –7.2; 7.7)
- Met key secondary endpoints of clinical outcomes at test of cure (TOC) defined as seven days after treatment, and Day 28 ACM:
- Clinical outcome at TOC: 64.8% (94/145) Fetroja versus 66.7% (98/147) meropenem high dose (difference: –2.0, 95% CI: –12.5; 8.5)
- Day 28 ACM: 22.1% (32/145) Fetroja versus 21.1% (31/147) meropenem high dose (difference: 1.1, 95% CI: –8.2; 10.4)
- 87.8% (130/148) for Fetroja versus 86.0% (129/150) for meropenem high dose (difference: 1.8; 95% CI: –5.8 to 9.5)
About Fetroja (cefiderocol) for injection
Fetroja® (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, Fetroja 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 Fetroja 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. Fetroja has also demonstrated in vitro activity against certain bacteria that contain very problematic resistant enzymes such as ESBLs, AmpC, serine- and metallo-carbapenemases. Data from multinational surveillance studies for Fetroja demonstrated potent in vitro activity against a wide spectrum of Gram-negative pathogens including carbapenem-resistant A. baumannii, P. aeruginosa, Enterobacterales, and S. maltophilia. The clinical significance of the in vitro data is unknown. Fetroja has poor in vitro activity against Gram-positive or anaerobic bacteria.
Cefiderocol, under the brand name FETCROJA®, is approved by the European Commission for the treatment of infections due to aerobic Gram-negative bacteria in adults 18 years or older with limited treatment options.
Indications from USPI
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, 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 susceptible bacteria.
Shionogi’s commitment to fighting antimicrobial resistance
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 research and development in anti-infectives. The company invests the highest proportion of its pharmaceutical revenues in relevant anti-infectives R&D compared to other large pharmaceutical companies.1
For more information please refer to: https://www.shionogi.com/global/en/sustainability/amr.html.
Shionogi & Co., Ltd. is a Japanese major research-driven pharmaceutical company 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, cardiovascular diseases, and gastroenterology. Our pipeline is focused on infectious disease, pain, CNS, and oncology. For more information on Shionogi & Co., Ltd., visit https://www.shionogi.com/global/en/. Shionogi Inc. is the U.S. subsidiary of Shionogi & Co., Ltd. based in N.J. For more information on Shionogi Inc., please visit www.shionogi.com.
Forward Looking Statement
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, unavailability 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.
1. Antimicrobial Resistance Benchmark 2020. https://accesstomedicinefoundation.org/media/uploads/downloads/5e270aa36821a_Antimicrobial_Resistance_Benchmark_2020.pdf. Last accessed July 2020.
Posted: September 2020
- FDA Approves Fetroja (cefiderocol) for the Treatment of Complicated Urinary Tract Infections – November 14, 2019
Fetroja (cefiderocol) FDA Approval History
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