Shionogi Receives European Commission Marketing Authorisation for FETCROJA® (cefiderocol) for the Treatment of Infections Due to Aerobic Gram-negative Bacteria in Adults With Limited Treatment Options
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.1
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 Enterobacterales2,3, as well as Stenotrophomonas maltophilia.6 Cefiderocol also demonstrated in vitro activity against certain bacteria that contain very problematic resistant enzymes such as ESBLs, AmpC, serine- and metallo-carbapenemases.7,8
Cefiderocol clinical trials
Data from three clinical studies: APEKS-cUTI and APEKS-NP and CREDIBLE-CR supported the marketing authorisation of cefiderocol.1 Data from the studies demonstrated the efficacy of cefiderocol in patients with the following types of infection: complicated urinary tract infections (cUTI) 9; hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), sepsis (including complicated intra-abdominal infection (cIAI) and skin and skin structure infection (SSSI)) and patients with bacteraemia (some with no identified primary focus of infection). One of the studies included patients with Gram-negative infections caused by multidrug-resistant pathogens including carbapenem-resistant bacteria from the WHO priority list.1
“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.”
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.10 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.4
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.”
Resistant Gram-negative infections
The increasing resistance of many infections caused by Gram-negative bacteria to existing therapies, including carbapenem-resistant Enterobacterales and non-fermenting species such as P. aeruginosa, A. baumannii, and S. maltophilia, makes them difficult to treat and results in high mortality rates.11 The World Health Organization have identified carbapenem-resistant strains of Enterobacterales, P. aeruginosa and A. baumannii as the top priority in the research and development of new antibiotics.2 Cefiderocol is the first antibiotic to address all three major mechanisms of carbapenem-resistance and is an important new treatment option to address this urgent unmet need.
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.
About Antimicrobial Resistance
Antimicrobial resistance (AMR) is a major health burden which urgently needs to be addressed. In Europe about 25,000 patients die from an infection with multidrug-resistant bacteria every year5. Infections caused by carbapenem-resistant Gram-negative bacteria are often associated with a high mortality rate12. 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.13
About cefiderocol access
Shionogi is committed to making Cefiderocol available as quickly as possible in the European Economic Area, to adult patients (18 years or older) with infections due to aerobic Gram-negative bacteria and limited treatment options
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: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Enterobacter cloacae complex.14
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.15
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 http://www.shionogi.co.jp/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 FETCROJA SMPC. Available at: https://www.shionogi.eu/media/418054/ema-combined-h-4829-en.pdf Last accessed April 2020
2 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 April 2020
3 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 April 2020
4 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
5 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 Last accessed April 2020
6 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. Antimicrob Agents Chemother. 2017 Sep; 61(9): e00093-17.
7 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). Int J Antimicrob Agents. 2019 Feb;53(2):177-184
8 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.
9 Portsmouth S, et al. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2018 Dec;18(12):1319-1328. doi: 10.1016/S1473-3099(18)30554-1.
10 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
11 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.
12 Perez F, et al. ‘Carbapenem-Resistant Enterobacteriaceae: A Menace to our Most Vulnerable Patients’. Cleve Clin J Med. Apr 2013; 80(4): 225–33
13 O’Neill J. ‘Tackling Drug-Resistant Infections Globally: Final Report and Recommendations’. Review on Antimicrobial Resistance. May 2016. https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf Last accessed April 2020
14 FETROJA (cefiderocol) FDA prescribing information. Florham Park, N.J. Shionogi Inc.: November 2019
15 Antimicrobial Resistance Benchmark 2020. https://accesstomedicinefoundation.org/media/uploads/downloads/5e270aa36821a_Antimicrobial_Resistance_Benchmark_2020 pdf Last accessed April 2020
For further information, contact:
Shionogi & Co., Ltd.
Shionogi Europe Media Contact
Dr. Mark Hill, Shionogi, firstname.lastname@example.org
Havas SO Media Contact
Senior Account Director
+44 (0)20 3196 9912
About Business Wire
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
bitFlyer Europe and Quazard Partner to Bring First Ever Trading Competition to Botwars Ultimate Trading1.6.2020 06:00:00 CEST | Press release
Leading cryptocurrency exchange bitFlyer, is partnering with crypto-trading game developer Quazard, to bring the first ever gamified trading competition to the Botwars Ultimate Trading universe. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200531005005/en/ bitFlyer and Quazard bring the first gamified trading competition to the Botwars Ultimate Trading universe (Graphic: Business Wire) The competition, which launches today, allows Botwars players to compete in a free to enter crypto-trading simulator to win real Bitcoin. This is the first trading competition to launch on Botwars, and the only live trading competition of its type. In Botwars Ultimate Trading, players need to build an army of trading robots (each representing a trade) and lead them into battle to conquer the cryptocurrency markets. Botwars is a real-time, gamified currency trading experience where you will learn new trading skills, unlock powerful new tradin
Celltrion Announces Positive Pre-clinical Results for COVID- 19 Antiviral Antibody Treatment, Showing Improvement in Recovery Time1.6.2020 03:00:00 CEST | Press release
Celltrion Group today announced positive pre-clinical results for its COVID-19 antiviral antibody treatment, with data demonstrating a 100-fold reduction in the viral load of SARS-CoV-2, the virus causing COVID-19. The treatment was also able to show improvement in lung lesions to a normal activity level in animal models. The pre-clinical study was conducted in an animal model in collaboration with one of the Korean National Universities, Chungbuk National University College of Medicine. The trial set out to assess the efficacy of two dosage amounts (low and high) for the antiviral antibody treatment. In comparison to the placebo-controlled group, the research team observed improved recovery in terms of clinical symptom scores such as runny nose, cough and body aches, after the first day of treatment. From the fifth day, significant clinical remission was observed. Reverse transcriptase polymerase chain reaction (RT-PCR) measurement and cell culture-based viral diagnosis were used to a
Idriverplus Joins the “Automate with Velodyne” Ecosystem29.5.2020 20:31:00 CEST | Press release
Velodyne Lidar, Inc. and Idriverplus today announced an expanded partnership and Idriverplus inclusion into the Automated with Velodyne integrator ecosystem, which helps companies grow their businesses while using Velodyne lidar technology. Through the program, Velodyne will further collaborate with Idriverplus to support its continued innovation and promote Idriverplus autonomous vehicles, including street cleaners, passenger cars and logistics vehicles. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200529005589/en/ Velodyne Lidar, Inc. and Idriverplus announced an expanded partnership and Idriverplus inclusion into the Automated with Velodyne integrator ecosystem, which helps companies grow their businesses while using Velodyne lidar technology. (Photo: Velodyne Lidar) Recently, Velodyne signed a multi-year sales agreement with Idriverplus to provide Puck™ sensors for the mass production of autonomous vehicles. Idriverplu
Interim Data from the Open Label Phase 2 OPTIC Study of Iclusig ® (ponatinib) for Chronic Phase-CML Presented at the ASCO and EHA Virtual Meetings29.5.2020 14:00:00 CEST | Press release
Incyte (Nasdaq:INCY) today announced that data from the interim analysis of the Phase 2 OPTIC (Optimizing Ponatinib Treatment In CML) trial, which was sponsored by Takeda and co-funded by Incyte, will be presented during an oral session at the upcoming 2020 American Society of Clinical Oncology Virtual Meeting (ASCO20; May 29 – May 31) (Abstract #7502)1; and at the virtual 25th Congress of the European Hematology Association (EHA25; June 11 – 14) (Abstract #S172)2. The OPTIC trial is an ongoing randomized, open-label study prospectively evaluating response-based dosing regimens of Iclusig® (ponatinib) over a range of three starting doses (45 mg, 30 mg, 15 mg) with the aim of optimizing its efficacy and safety in patients with chronic-phase chronic myeloid leukemia (CP-CML), who are resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. With a median follow up of approximately 21 months, data from the interim analysis of the OPTIC trial show that the optimal benefit-r
Takeda to Present Data from the ICLUSIG ® (ponatinib) Clinical Trial Program that Could Prove Practice-Changing for the Treatment of Chronic-Phase CML29.5.2020 14:00:00 CEST | Press release
Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) today announced that interim analysis data from the Phase 2 OPTIC (Optimizing Ponatinib Treatment In CML) trial will be presented during an oral session at the virtual 56thAmerican Society of Clinical Oncology (ASCO) Annual Meeting and the 25thEuropean Hematology Association (EHA) Annual Meeting. The OPTIC trial is an ongoing, randomized, open-label study prospectively evaluating response-based dosing regimens of ICLUSIG® (ponatinib) over a range of three starting doses (45-, 30-, or 15-mg) with the aim of optimizing its efficacy and safety in patients with chronic-phase chronic myeloid leukemia (CP-CML) who are resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. With a median follow-up of approximately 21 months, data from the interim analysis of OPTIC show that the optimal benefit-risk profile for ICLUSIG in patients with CP-CML is achieved with a daily starting dose of 45-mg and, upon achieving ≤1% BCR-A
Takeda Receives Positive CHMP Opinion for Pre-Filled Syringe Presentation of TAKHZYRO ® (lanadelumab) for Use as a Preventive Treatment for Hereditary Angioedema Attacks29.5.2020 14:00:00 CEST | Press release
Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion on a Type II Variation regulatory application and recommended the approval of a pre-filled syringe presentation of TAKHZYRO® (lanadelumab). TAKHZYRO is a subcutaneous injectable prescription medication approved in Europe for routine prevention of recurrent attacks of hereditary angioedema (HAE) in patients aged 12 years and older. HAE is a rare genetic disorder that results in recurrent attacks of oedema – swelling – in various parts of the body, including the abdomen, face, feet, genitals, hands and throat.1,2,3 “Our goal is to continuously innovate in all areas of HAE management,” said Isabel Kalofonos, Global Product Strategy Lead, HAE, Takeda. “This positive opinion marks another important step forward as we aim to enhance the experience of treatment administration for peo
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