Shionogi Announces Publication of Two Studies in the Lancet Infectious Diseases Highlighting the Efficacy and Safety of Cefiderocol for the Treatment of Infections Due to Aerobic Gram-negative Bacteria in Adults With Limited Treatment Options
FOR MEDICAL AND PHARMA TRADE MEDIA ONLY
Shionogi & Co., Ltd. (Head Office: Osaka, Japan; President & CEO: Isao Teshirogi, Ph.D.) (hereafter "Shionogi") today announces the back to back publication of two studies in The Lancet Infectious Diseases journal highlighting the efficacy and safety of cefiderocol against some of the most difficult-to-treat Gram-negative bacterial infections, including nosocomial pneumonia (NP), bloodstream infections (BSI), sepsis, and complicated urinary tract infections (cUTI).1,2
APEKS-NP was a Phase 3 clinical trial designed to compare the efficacy and safety of cefiderocol versus high-dose, extended-infusion meropenem (2g, q8h, 3-hour infusion) in critically ill patients with hospital-acquired, ventilator-associated, or healthcare-associated pneumonia (HAP, VAP, and HCAP, respectively) caused by a broad range of Gram-negative bacteria, like Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales, including patients at risk of MDR infections. The study successfully met the primary endpoint of non-inferiority in all-cause mortality (ACM) at Day 14 with 12.4% for the cefiderocol arm (18/145) and 11.6% for the meropenem arm (17/146; adjusted treatment difference 0.8% [95% CI –6.6 to 8.2]) in the modified intention-to treat-population (mITT population). Cefiderocol was well tolerated, and its safety profile was consistent with that of other cephalosporins and/or carbapenems.1
The CREDIBLE-CR trial was a small non-inferential Phase 3 open label, pathogen-focused trial designed to assess the efficacy and safety of cefiderocol or best available therapy (BAT) for the treatment of a diverse range of serious CR infections including CR non-fermenters and carbapenemase producers consisting of NP, BSI, sepsis, and cUTI. BAT was combination therapy in 71% (27/38) of cases with 28 different BAT regimens being used, whereas 83% (66/80) of cefiderocol treatment was monotherapy. Two thirds (66% [25/38]) of the BAT regimens contained colistin.2
The results of the CREDIBLE-CR study provided descriptive evidence of the efficacy and safety of cefiderocol in CR Gram-negative infections in a highly heterogeneous patient population frequently presenting with complex comorbidities. The clinical and microbiological outcomes were generally similar between cefiderocol and BAT, except for metallo-beta-lactamases infections where cefiderocol was substantially better (cefiderocol: 75% and 44%; BAT: 29% and 14%, respectively). There was an observed mortality difference between treatment arms in the subset of patients with Acinetobacter spp. infections, likely linked to imbalances in risk factors at baseline. There was no mortality difference observed in P. aeruginosa or Enterobacterales without Acinetobacter spp. co-infection. No deaths were attributed to cefiderocol-related adverse events as examined by investigators assessing the mortality imbalance.2
“The patient population in the CREDIBLE-CR study represents a real clinical scenario with the highest unmet need and provides descriptive evidence that cefiderocol may be a treatment option for physicians treating such critically ill patients,” commented Professor Matteo Bassetti, Lead Author and Head of the Infectious Diseases Clinic, San Martino Hospital, Genoa, Italy.
“From the results of APEKS-NP and CREDIBLE-CR studies, we believe that cefiderocol becomes a new option for the treatment of patients at risk of multi-drug resistant Gram-negative infections”, said Takuko Sawada, Director and Executive Vice President, Senior Vice President of Integrated Disease Care Department of Shionogi.
Cefiderocol received European Commission (EC) marketing authorisation for the treatment of infections due to aerobic Gram-negative bacteria in adults with limited treatment options under the brand name FETCROJA® in April 2020 and is now commercially available in the UK. Shionogi remains committed to making the drug available further in Europe as quickly as possible.6
Cefiderocol is the first treatment which provides coverage against all Gram-negative pathogens considered of critical priority by the WHO – carbapenem -resistant A. baumannii, P. aeruginosa, and Enterobacterales.3,4
Antimicrobial resistance (AMR)
Antimicrobial resistance (AMR) is a major health burden which urgently needs to be addressed. Globally, approximately 700,000 people die as a result of infections caused by resistant pathogens every year. Infections caused by carbapenem-resistant Gram-negative bacteria are often associated with a high mortality rate.7 If no action is taken, antibiotic resistance is predicted to kill 10 million people every year by 2050, at a cumulative cost to global economic output of 100 trillion USD.5
About FETCROJA® (cefiderocol)
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, 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.8 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.9 Cefiderocol has also demonstrated in vitro activity against certain bacteria that contain very problematic resistant enzymes such as ESBLs, AmpC, serine- and metallo-carbapenemases.10,11 Data from multinational surveillance studies for cefiderocol demonstrated potent in vitro activity against a wide spectrum of Gram-negative pathogens including carbapenem-resistant A. baumannii, P. aeruginosa, Enterobacterales, and Stenotrophomonas maltophilia.12 The clinical significance of the in vitro data is unknown. Cefiderocol has no clinically relevant activity against Gram-positive or anaerobic bacteria.
Cefiderocol is commercially available in the U.S after approval by the FDA in 2019 under the brand name FETROJA® 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: E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa, and E. cloacae complex.13
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.14
For more information please refer to: https://www.shionogi.com/global/en/sustainability/amr.html
Shionogi & Co., Ltd. is a 142-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 B.V. is the European headquarters of Shionogi & Co., Ltd. For more information on Shionogi B.V., please visit www.shionogi.eu.
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.
© 2020 Shionogi Europe. London, WC2B 6UF. All Rights Reserved.
1 Wunderrink RG et al, Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): a Phase 3, randomised, double-blind, non-inferiority study, The Lancet Infectious Diseases 2020. Available at: https://doi.org/10.1016/S1473-3099(20)30731-3. Last accessed October 2020
2 Bassetti M, Efficacy and safety of cefiderocol for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): results of a Phase 3 randomised, open-label, parallel-assigned, pathogen-focused study, The Lancet Infectious Diseases 2020. Available at: https://doi.org/10.1016/S1473-3099(20)30796-9. Last accessed October 2020
3 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/. Last accessed July 2020
4 World Health Organization. 2019 Antibacterial Agents in Clinical Development. 2019. Retrieved from
https://apps.who.int/iris/bitstream/handle/10665/330420/9789240000193-eng.pdf Last accessed July 2020
5 O’Neill, J. et al. Review on antimicrobial resistance. Tackling drug-resistant infections globally: final report and recommendations. 2016 https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf Last accessed July 2020
7 Perez F, et al. ‘Carbapenem-Resistant Enterobacteriaceae: A Menace to our Most Vulnerable Patients’. Cleve Clin J Med. Apr 2013; 80(4): 225–33
8 Ito A, Nishikawa T., Masumoto S, et al. Siderophore Cephalosporin Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial Activity against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2016;60(12):7396-7401
9 Tillotson GS. Trojan Horse Antibiotics—A Novel Way to Circumvent Gram-Negative Bacterial Resistance? Infectious Diseases: Research and Treatment. 2016;9:45-52 doi:10.4137/IDRT.S3156
10 K Kazmierczak et al. In vitro activity of cefiderocol, a siderophore cephalosporin, against a recent collection of clinically relevant carbapenem-non-susceptible Gram-negative bacilli, including serine carbapenemase- and metallo-β-lactamase-producing isolates (SIDERO-WT-2014 Study). ). International Journal of Antimicrobial Agents, 2019; 53(2) 177-184
11 A Ito et al. In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrobial Agents and Chemotherapy, 2018, 62:e01454-17.
12 M Hackel, M Tsuji, Y Yamano, 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. Antimicrobial Agents Chemotherapy. 2017;61(9)
13 FETROJA (cefiderocol) prescribing information. Florham Park, N.J. Shionogi Inc.: November 2019
14 Antimicrobial Resistance Benchmark 2020.
https://accesstomedicinefoundation.org/media/uploads/downloads/5e270aa36821a_Antimicrobial_Resistance_Benchmark_2020 pdf Last accessed July 2020
For further information, contact:
Shionogi & Co., Ltd.
Shionogi Europe Media Contact
Dr. Mark Hill, Shionogi
Havas SO Media Contact
Senior Account Director
+44 (0)20 3196 9912
About Business Wire
For more than 50 years, Business Wire has been the global leader in press release distribution and regulatory disclosure.
Subscribe to releases from Business Wire
Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.
Latest releases from Business Wire
Verimatrix Video Content Security Expert to Speak at SportsPro Asia Virtual Summit20.10.2020 18:45:00 EEST | Press release
Regulatory News: Verimatrix, (Paris:VMX) (Euronext Paris: VMX), the leader in powering the modern connected world with people-centered security, today announced that Christopher Rae, Senior Vice President of Sales for Asia Pacific, is scheduled to speak during a SportsPro Asia panel discussion at 4 p.m. SGT on Thursday, October 22. Titled, “Reimagining the Fan Experience: Maximizing Opportunities Through Digital”, the panel is set to discuss how OTT and digital bring the promise of personalized, responsive viewer experiences that go far beyond those of linear broadcast platforms. The panel will also discuss the latest piracy threats and challenges associated with launching new streaming services in different Asian markets. Rae’s fellow panelists include: Jay Ganesan, Senior Vice President and Region Head for Asia Pacific at MediaKind Oliver Duss, Executive Vice President, Media, at Football Marketing Asia (FMA) Eoin Connolly, Editor At Large at SportsPro SportsPro Asia provides attende
Nexeo Plastics Signs Distribution Agreement in Europe with Kingfa20.10.2020 17:06:00 EEST | Press release
Nexeo Plastics, a leading global thermoplastics resin distributor, has signed an agreement with Kingfa to distribute their engineering thermoplastic products throughout Europe. Effective immediately, Nexeo Plastics will carry and distribute Kingfa’s locally made compounds. Each product group offers a wide range of color-matching options and innate characteristics to improve manufacturing and end-product functionality. This includes an array of choices in unfilled, talc-filled, reinforced, toughened, flame-retardant and recycled compounds. “We look forward to partnering with Nexeo Plastics to expand our footprint in Europe and reach new customers who are seeking high-quality, customized compounding solutions,” said Dr. D.H. Sun, managing director of Kingfa Europe. Kingfa, a preeminent leader in the research, production and sales of advanced polymer materials, has European facilities in Wiesbaden, Germany, serving the EMEA region. The location includes an advanced technology production p
Brookfield Renewable Ireland Selects PCI’s Enterprise Cloud Platform to Meet its Energy Billing Requirements20.10.2020 17:00:00 EEST | Press release
Brookfield Renewable Ireland has selected PCI’s Enterprise Platform for management of its energy billing requirements in the Irish power market. As part of its agreement with Brookfield Renewable Ireland, PCI will deploy its specifically tailored, cloud-based, integrated platform that incorporates the PCI Billing Solution, and a breadth of capabilities including: Management of complex bilateral contracts, such as power purchase agreements (PPA) Contract settlements calculation engine to perform settlement allocation based on specific business rules Interfaces with upstream and downstream systems Comprehensive auditability with all data versions and updates stored for auditing requirements Extensive workflow automation for invoice creation and management Data extraction, reporting and drill-down capabilities Platform extension to support Brookfield Renewable Ireland’s customer portal Chief Commercial Officer at Brookfield Renewable Ireland, Ciaran O'Brien noted, “To support our business
Goldman Sachs Merchant Banking Division Partners With Leading Data Infrastructure Management Team and Commits up to $500 Million to Form Data Center Platform, Global Compute20.10.2020 17:00:00 EEST | Press release
The Goldman Sachs Merchant Banking Division (“GS MBD”) today announced that it has partnered with a seasoned management team, led by long-time data center industry executive Scott Peterson, to form Global Compute Infrastructure LP (“Global Compute” or the “Company”), a newly established global data center infrastructure platform. GS MBD has initially committed to fund up to $500 million of equity capital, primarily from its infrastructure fund, West Street Infrastructure Partners III, LP (“WSIP III”), to enable approximately $1.5 billion in near-term investments deployed across North America, Europe, Asia Pacific and Latin America. Global Compute intends to grow through a combination of acquisitions and organic development to serve customers in geographies with strong secular tailwinds and potential for significant data infrastructure growth. Leveraging the experience and track record of the management team, Global Compute will focus on acquiring and developing facilities which can mee
Andersen Global Signs Collaboration Agreement with Belarus’ Largest Law Firm20.10.2020 16:30:00 EEST | Press release
Andersen Global expands its platform in Eastern Europe with the addition of collaborating firm REVERA, one of the top tier law firms in Belarus, broadening the organization’s coverage as it bolsters its foothold in the region. Founded in 1998, the Minsk-based firm provides corporate, commercial, litigation, labor, antitrust, real estate and intellectual property law, focusing on tax and private client services. Led by Managing Partner Dmitry Arkhipenko, REVERA’s team of more than 50 lawyers represents a number of multinational companies and often participates in Belarus’ legislative process. Additionally, the firm has been recognized by Chambers Europe, Legal 500, IFLR 100 and Best Lawyers. “For over 20 years, our firm has built a respectable reputation through our commitment to stewardship and independence, and our ability to provide clients with best-in-class solutions,” Dmitry said. “We look forward to working with the member firms and collaborating firms of Andersen Global as we co
The 26th China Yiwu International Commodities (Standards) Fair to Kick Off This Month With More Activities to Promote Trade20.10.2020 16:21:00 EEST | Press release
The 26th China Yiwu International Commodities (Standards) Fair ("Yiwu Fair") will be held at Yiwu International Expo Center on October 21-25, 2020. Founded in 1995 and as one of the three export exhibitions sponsored by China’s Ministry of Commerce, Yiwu Fair is now the largest, most influential, and most effective daily necessities exhibition in China. Yiwu Fair 2020 will be China’s first large-scale foreign trade exhibition presented both online and offline in the wake of the pandemic. It is expected to attract more than 50,000 professional buyers, with 3,400 international standard booths, covering hardware, electromechanical facilities, electronic & electrical appliances, daily necessities, crafts & ornaments, stationery & office goods, toys, sporting & outdoor products, knitwear, and gift packaging. This year, Yiwu Fair will invite around 10 delegations or 1,600 persons from foreign trade organizations and representative offices based in China, and nearly 20 delegations or 1,800 bu
In our pressroom you can read all our latest releases, find our press contacts, images, documents and other relevant information about us.Visit our pressroom