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Shionogi Announces Submission of Cefiderocol Marketing Authorisation Application

OSAKA, Japan & AMSTERDAM, NL–(BUSINESS WIRE)–Shionogi & Co., Ltd (hereafter “Shionogi”) announces that the Marketing
Authorisation Application (MAA) submission for cefiderocol, a novel
siderophore cephalosporin, has been accepted for review by the European
Medicines Agency (EMA). The CHMP has granted cefiderocol accelerated
assessment indicating that this medication is expected to be of major
public health interest, particularly from the point of view of
therapeutic innovation. Shionogi is seeking an indication for the
treatment of infections due to aerobic Gram-negative bacteria in adult
patients with limited treatment options.

Cefiderocol has shown in vitro activity against all the
Gram-negative species that were identified by the WHO as being the
highest priority for finding new treatments.1,2 These include
the critical carbapenem-resistant Gram-negative non-fermenters Acinetobacter
baumannii, Pseudomonas aeruginosa
, as well as difficult-to-treat
carbapenem-resistant Enterobacteriaceae. Cefiderocol has been
developed to meet a significant unmet need in an area where mortality is
high. No antibiotics are currently available that address all three
major carbapenem-resistant mechanisms.

We are pleased to announce the MAA submission for cefiderocol which
is an important milestone in the regulatory process.
” said Dr. John
Keller Senior Vice President Global Business Division and Head of
European and US operations Shionogi.

AMR (Antimicrobial Resistance) is a major health burden that urgently
needs to be addressed. In the US and Europe alone, approximately 56,000
people die of antibiotic-resistant infections every year.3,4 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 Cefiderocol – An Investigational Antibiotic Agent

Cefiderocol is a siderophore cephalosporin with a novel mechanism for
efficiently penetrating the outer cell membrane of Gram-negative
pathogens. 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.6 This mechanism allows cefiderocol to overcome
resistance due to porin channel mutations as well as achieving higher
concentrations in the periplasmic space where it can then bind to
receptors and inhibit cell wall synthesis in the bacterial cells.7
In addition, cefiderocol can also enter cells by passive diffusion
through porin channels and is stable against all known classes of
beta-lactamases, including both the metallo- and serine-carbapenemases.8
Data from global surveillance studies for cefiderocol demonstrated
potent in vitro activity against a wide spectrum of Gram-negative
pathogens including carbapenem-resistant Acinetobacter baumannii, P.
aeruginosa
, Enterobacteriaceae, and S. maltophilia.1
Cefiderocol has poor in vitro activity against
Gram-positive or anaerobic bacteria.

Cefiderocol is currently in clinical development. The APEKS-cUTI study
was successfully completed in 2017. It was a multinational, multicenter,
double-blind trial, which enrolled 452 patients with a complicated
urinary tract infection (cUTI). This trial was designed to evaluate the
efficacy and safety of cefiderocol in this population versus
imipenem/cilastatin in hospitalized adult patients at risk for
multidrug-resistant Gram-negative infection.9,10,11 The
Lancet Infectious Diseases
journal has published the clinical
results from this trial.12

Two Phase III studies are ongoing in patients with HAP/VAP/HCAP
(APEKS-NP) and with carbapenem-resistant pathogens at various infection
sites (CREDIBLE-CR). Information is available at www.clinicaltrials.gov under
the identifiers NCT02714595 and NCT03032380, respectively.

Shionogi & Co., Ltd. (“Shionogi”) 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, 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, please visit http://www.shionogi.co.jp/en/.

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.

© 2019 Shionogi Limited. London, WC2B 6UF. All Rights Reserved.

References

1 M Hackel, M Tsuji, Y Yamano, et al. n 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), posted online.

2 WHO. WHO publishes list of bacteria for which new
antibiotics are urgently needed https://www.who.int/en/news-room/detail/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed

3 CDC. Antibiotic / Antimicrobial Resistance (AR / AMR).
Available at: https://www.cdc.gov/drugresistance/index.html
Last accessed March 2019

4 European Commission. EU Action on Antimicrobial Resistance.
Available at: http://ec.europa.eu/health/amr/antimicrobial-resistance_en
Last accessed March 2019

5 O’Neill, J. et al. Review on antimicrobial
resistance. Tackling drug-resistant infections globally: final report
and recommendations. 2016

6 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.

7 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.S31567

8 Ito-Horiyama T, Ishii Y, Ito A, et al. Stability of Novel
Siderophore Cephalosporin S-649266 against Clinically Relevant
Carbapenemases. Antimicrob Agents Chemother.
2016;60(7):4384-4386.

9 Press
release on January 12,2017

SHIONOGI ANNOUNCES POSITIVE TOP-LINE
RESULTS FOR CEFIDEROCOL PIVOTAL cUTI CLINICAL TRIAL

10 Press
release on April 25,2017

Shionogi Presents Results of the First
Clinical Efficacy Trial and In Vitro Data on Cefiderocol (S-649266), a
Siderophore Cephalosporin

11 Press
release on October 5,2017

SHIONOGI PRESENTS POSITIVE CLINICAL
EFFICACY TRIAL RESULTS AND IN VITRO DATA ON CEFIDEROCOL, AT
IDWEEK 2017

12 Press
release on October 25,2018

Pivotal Trial Results for Shionogi’s
Cefiderocol Published in The Lancet Infectious Diseases

Contacts

Corporate Communications Department
Shionogi & Co., Ltd.
Telephone:
+81-6-6209-7885

Shionogi Europe Media Contact
Russell
Stapley
European Antimicrobial Franchise lead
+44 (0) 7741
626375
[email protected]

Havas
So Media Contact

Jessica Stuart
Account Manager
+44
(0) 20 3196 8772
[email protected]

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