FETROJA is the first approved antibiotic that functions as a siderophore
FETROJA binds to free iron to gain additional cell entry
FETROJA demonstrated higher response rates versus imipenem/cilastatin in a cUTI study
OSAKA, Japan & FLORHAM PARK, NJ, USA I November 14, 2019 I Shionogi & Co., Ltd. (hereafter “Shionogi”) today announced the U.S. Food and Drug Administration (FDA) has approved FETROJA® (cefiderocol) for patients 18 years of age or older who have limited or no alternative treatment options, for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following: susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Enterobacter cloacae complex. Approval of this indication is based on limited clinical safety and efficacy data for FETROJA.
“FETROJA will fill a very important unmet medical need because of its unique method of penetrating the cell wall of Gram-negative bacteria and its ability to overcome many of the resistance mechanisms that bacteria employ against antibiotics. Today’s approval represents 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 Isao Teshirogi, Ph.D., president and CEO at Shionogi.
The approval of FETROJA is based on data from the pivotal APEKS-cUTI study, a multinational, multicenter, double-blind clinical trial that evaluated the efficacy and safety of FETROJA versus imipenem/cilastatin (IPM/CS) in patients with cUTI. Study results showed the response rates for the composite endpoint of microbiological eradication and clinical response at the test of cure (TOC) were significantly higher in the FETROJA arm compared to the IPM/CS arm. In the study, 72.6% (183/252) of patients in the FETROJA arm met the primary endpoint versus 54.6% (65/119) in the IPM/CS arm at TOC. The adjusted difference between the groups was 18.58% (95% CI: 8.2%, 28.2%). Clinical response rates at the TOC visit were similar between FETROJA and IPM/CS.
Serious adverse events were reported for 4.7% (14/300) of patients who received FETROJA and 8.1% (12/148) of patients who received IPM/CS. The most frequently occurring adverse reactions in greater than or equal to 2% of patients treated with FETROJA were diarrhea, infusion site reactions, constipation, rash, candidiasis, cough, elevations in liver tests, headache, hypokalemia, nausea, and vomiting. Please see Important Safety Information, Indications and Usage below.
“In the pivotal study, cefiderocol achieved a higher response rate compared to imipenem/cilastatin,” said George H. Karam, M.D., MACP, Paula Garvey Manship Chair of Medicine at the Louisiana State University School of Medicine. “With today’s approval of cefiderocol, the infectious disease community now has a new type of antibiotic with a unique mechanism of cell entry to add to their toolkit to assist in the complexity of treating highly resistant pathogens that are occurring with increasing frequency in life-threatening infections.”
FETROJA was designated a Qualified Infectious Disease Product (QIDP) by the FDA, providing Fast Track designation and Priority Review. Shionogi anticipates making FETROJA commercially available in early 2020.
About Gram-negative Infections
The increasing resistance of many infections caused by Gram-negative bacteria to existing therapies, including carbapenem-resistant Enterobacteriaceae and non-fermenting species such as Pseudomonas aeruginosa (P. aeruginosa), Acinetobacter baumannii (A. baumannii), and Stenotrophomonas maltophilia (S. maltophilia), poses a serious health challenge.1-5 There is an increasing number of Gram-negative pathogens resistant to multiple antibiotics, making them difficult to treat and resulting in high mortality rates.6 In the U.S., More than 2.8 million antibiotic-resistant infections occur in the United States each year, and more than 35,000 people die as a result.7 In the EU, about 25,000 patients die from an infection with the selected multidrug-resistant bacteria.8 The World Health Organization and the Centers for Disease Control and Prevention have identified carbapenem-resistant strains of Enterobacteriaceae, P. aeruginosa, and A.baumannii as the top priority in the research and development of new antibiotics.2,7
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.13 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.13 FETROJA has also demonstrated in vitro activity against certain bacteria that contain very problematic resistant enzymes such as ESBLs, AmpC, serine- and metallo-carbapenemases.13 Data from multinational surveillance studies for FETROJA demonstrated potent in vitro activity against a wide spectrum of Gram-negative pathogens including carbapenem-resistant Acinetobacter baumannii (A. baumannii), Pseudomonas aeruginosa (P. aeruginosa), Enterobacteriaceae, and Stenotrophomonas maltophilia (S. maltophilia).1 The clinical significance of the in vitro data is unknown. FETROJA has poor in vitro activity against Gram-positive or anaerobic bacteria.
Shionogi also submitted a marketing authorization application for cefiderocol to the European Medicines Agency and it was accepted in March 2019.10
Indication
FETROJA® (cefiderocol) is indicated in patients 18 years of age or older who have limited or no alternative treatment options for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Enterobacter cloacae complex.
Approval of this indication is based on limited clinical safety and efficacy data for FETROJA.
Usage
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. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
For full Prescribing Information, please visit Shionogi.com.
References
- Hackel M, Tsuji M, Yamano Y, et al. In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, Against a Recent Collection of Clinically Relevant Gram-Negative Bacilli from North America and Europe, Including Carbapenem Non-Susceptible Isolates: The SIDERO-WT-2014 Study. Antimicrob Agents Chemother. 2017;61(9):e00093−17. doi.org/10.1128/AAC.00093-17.
- World Health Organization. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. February 27, 2017. Retrieved from https://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en/.
- Diene SM, Rolain JM. Carbapenemase genes and genetic platforms in gram-negative bacilli: Enterobacteriaceae, Pseudomonas and Acinetobacter species. Clin Microbiol Infect 2014; 20:831−38.
- Livermore DM. Current epidemiology and growing resistance of gram-negative pathogens. Korean J Intern Med 2012; 27:128−42.
- Brooke JS. Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev 2012; 25:2−41.
- Tangden T, Giske CG. Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control. J Intern Med 2015; 277:501−12.T.
- Centers for Disease Control and Prevention (CDC). Antibiotic Resistance Threats in the United States 2019, Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019. Retrieved from https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf
- European Centre for Disease Prevention and Control (ECDC). Technical Report: the bacterial challenge: time to react. 2009. Retrieved from
https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf.
- FETROJA® (cefiderocol) prescribing information. Florham Park, N.J. Shionogi Inc.: November 2019.
- Shionogi & Co, Ltd. Shionogi announces submission of cefiderocol marketing authorisation application. April 1, 2019. Retrieved from http://www.shionogi.co.jp/en/company/news/2019/pmrltj000000418y-att/e_190401_2.pdf.
SOURCE: Shionogi
Post Views: 226
FETROJA is the first approved antibiotic that functions as a siderophore
FETROJA binds to free iron to gain additional cell entry
FETROJA demonstrated higher response rates versus imipenem/cilastatin in a cUTI study
OSAKA, Japan & FLORHAM PARK, NJ, USA I November 14, 2019 I Shionogi & Co., Ltd. (hereafter “Shionogi”) today announced the U.S. Food and Drug Administration (FDA) has approved FETROJA® (cefiderocol) for patients 18 years of age or older who have limited or no alternative treatment options, for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following: susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Enterobacter cloacae complex. Approval of this indication is based on limited clinical safety and efficacy data for FETROJA.
“FETROJA will fill a very important unmet medical need because of its unique method of penetrating the cell wall of Gram-negative bacteria and its ability to overcome many of the resistance mechanisms that bacteria employ against antibiotics. Today’s approval represents 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 Isao Teshirogi, Ph.D., president and CEO at Shionogi.
The approval of FETROJA is based on data from the pivotal APEKS-cUTI study, a multinational, multicenter, double-blind clinical trial that evaluated the efficacy and safety of FETROJA versus imipenem/cilastatin (IPM/CS) in patients with cUTI. Study results showed the response rates for the composite endpoint of microbiological eradication and clinical response at the test of cure (TOC) were significantly higher in the FETROJA arm compared to the IPM/CS arm. In the study, 72.6% (183/252) of patients in the FETROJA arm met the primary endpoint versus 54.6% (65/119) in the IPM/CS arm at TOC. The adjusted difference between the groups was 18.58% (95% CI: 8.2%, 28.2%). Clinical response rates at the TOC visit were similar between FETROJA and IPM/CS.
Serious adverse events were reported for 4.7% (14/300) of patients who received FETROJA and 8.1% (12/148) of patients who received IPM/CS. The most frequently occurring adverse reactions in greater than or equal to 2% of patients treated with FETROJA were diarrhea, infusion site reactions, constipation, rash, candidiasis, cough, elevations in liver tests, headache, hypokalemia, nausea, and vomiting. Please see Important Safety Information, Indications and Usage below.
“In the pivotal study, cefiderocol achieved a higher response rate compared to imipenem/cilastatin,” said George H. Karam, M.D., MACP, Paula Garvey Manship Chair of Medicine at the Louisiana State University School of Medicine. “With today’s approval of cefiderocol, the infectious disease community now has a new type of antibiotic with a unique mechanism of cell entry to add to their toolkit to assist in the complexity of treating highly resistant pathogens that are occurring with increasing frequency in life-threatening infections.”
FETROJA was designated a Qualified Infectious Disease Product (QIDP) by the FDA, providing Fast Track designation and Priority Review. Shionogi anticipates making FETROJA commercially available in early 2020.
About Gram-negative Infections
The increasing resistance of many infections caused by Gram-negative bacteria to existing therapies, including carbapenem-resistant Enterobacteriaceae and non-fermenting species such as Pseudomonas aeruginosa (P. aeruginosa), Acinetobacter baumannii (A. baumannii), and Stenotrophomonas maltophilia (S. maltophilia), poses a serious health challenge.1-5 There is an increasing number of Gram-negative pathogens resistant to multiple antibiotics, making them difficult to treat and resulting in high mortality rates.6 In the U.S., More than 2.8 million antibiotic-resistant infections occur in the United States each year, and more than 35,000 people die as a result.7 In the EU, about 25,000 patients die from an infection with the selected multidrug-resistant bacteria.8 The World Health Organization and the Centers for Disease Control and Prevention have identified carbapenem-resistant strains of Enterobacteriaceae, P. aeruginosa, and A.baumannii as the top priority in the research and development of new antibiotics.2,7
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.13 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.13 FETROJA has also demonstrated in vitro activity against certain bacteria that contain very problematic resistant enzymes such as ESBLs, AmpC, serine- and metallo-carbapenemases.13 Data from multinational surveillance studies for FETROJA demonstrated potent in vitro activity against a wide spectrum of Gram-negative pathogens including carbapenem-resistant Acinetobacter baumannii (A. baumannii), Pseudomonas aeruginosa (P. aeruginosa), Enterobacteriaceae, and Stenotrophomonas maltophilia (S. maltophilia).1 The clinical significance of the in vitro data is unknown. FETROJA has poor in vitro activity against Gram-positive or anaerobic bacteria.
Shionogi also submitted a marketing authorization application for cefiderocol to the European Medicines Agency and it was accepted in March 2019.10
Indication
FETROJA® (cefiderocol) is indicated in patients 18 years of age or older who have limited or no alternative treatment options for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Enterobacter cloacae complex.
Approval of this indication is based on limited clinical safety and efficacy data for FETROJA.
Usage
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. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
For full Prescribing Information, please visit Shionogi.com.
References
- Hackel M, Tsuji M, Yamano Y, et al. In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, Against a Recent Collection of Clinically Relevant Gram-Negative Bacilli from North America and Europe, Including Carbapenem Non-Susceptible Isolates: The SIDERO-WT-2014 Study. Antimicrob Agents Chemother. 2017;61(9):e00093−17. doi.org/10.1128/AAC.00093-17.
- World Health Organization. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. February 27, 2017. Retrieved from https://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en/.
- Diene SM, Rolain JM. Carbapenemase genes and genetic platforms in gram-negative bacilli: Enterobacteriaceae, Pseudomonas and Acinetobacter species. Clin Microbiol Infect 2014; 20:831−38.
- Livermore DM. Current epidemiology and growing resistance of gram-negative pathogens. Korean J Intern Med 2012; 27:128−42.
- Brooke JS. Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev 2012; 25:2−41.
- Tangden T, Giske CG. Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control. J Intern Med 2015; 277:501−12.T.
- Centers for Disease Control and Prevention (CDC). Antibiotic Resistance Threats in the United States 2019, Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019. Retrieved from https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf
- European Centre for Disease Prevention and Control (ECDC). Technical Report: the bacterial challenge: time to react. 2009. Retrieved from
https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf.
- FETROJA® (cefiderocol) prescribing information. Florham Park, N.J. Shionogi Inc.: November 2019.
- Shionogi & Co, Ltd. Shionogi announces submission of cefiderocol marketing authorisation application. April 1, 2019. Retrieved from http://www.shionogi.co.jp/en/company/news/2019/pmrltj000000418y-att/e_190401_2.pdf.
SOURCE: Shionogi
Post Views: 226
