Shionogi to Present New Data at IDWeek 2019

September 26, 2019 Off By BusinessWire

– Including Cefiderocol Phase III APEKS-NP Trial as Late-breaker Oral Presentation –

OSAKA, Japan & FLORHAM PARK, N.J.–(BUSINESS WIRE)–Shionogi & Co., Ltd. (hereafter “Shionogi”) today announced that the company will deliver 20 data presentations for Shionogi compounds, including a late-breaker oral presentation of cefiderocol Phase III APEKS-NP trial results, at IDWeek™, October 2-6, 2019, in Washington, D.C.

Cefiderocol is a siderophore cephalosporin with a novel mechanism for penetrating the outer cell membrane of Gram-negative pathogens including multidrug-resistant strains. At IDWeek, Shionogi will share findings from the APEKS-NP trial evaluating the investigational antibiotic cefiderocol in adults with hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, or healthcare-associated bacterial pneumonia caused by Gram-negative pathogens. Additionally, Shionogi will share findings from other studies investigating cefiderocol, and the prevalence and characterization of carbapenem-resistant bacterial infections.

The company will also present data for XOFLUZA^™ (baloxavir marboxil), a first-in-class, one-dose oral medicine for the treatment of acute uncomplicated influenza in patients 12 years of age and older who have been symptomatic for no more than 48 hours.

“This is the first release of data from the Phase III APEKS-NP trial. The results strengthen our belief that cefiderocol has the potential to make a meaningful difference for patients fighting life-threatening Gram-negative infections,” said Dr. Tsutae “Den” Nagata, Chief Medical Officer, Shionogi.

Presentations will include data from company-sponsored or investigator-initiated investigational studies. The details for the presentations are as follows:

Oral presentation about cefiderocol

Oral presentation #LB4: Efficacy and Safety of Cefiderocol versus High-Dose Meropenem in Patients with Nosocomial Pneumonia – Results of a Phase 3 Randomized, Multicenter, Double-Blind, Non-Inferiority Study

Date and time: October 3, 2:15-2:25 p.m.

Session title and location: Late Breaker Oral Abstract Session 1; Room 209 ABC of the Walter E. Washington Convention Center

All poster presentations will take place on the following dates and times; session titles and location:

Cefiderocol

Date and time: October 3, 12:15 p.m.-1:30 p.m.

Location: Poster Hall at the Walter E. Washington Convention Center

Session title: Bacteremia, CLABSI, and Endovascular Infections

Poster #164: Analysis of Adult, Hospitalized Patients with Carbapenem-resistant (CR) Gram-negative Bloodstream Infections (GN-BSIs) due to Lactose Fermenters (LFs) and Non-Lactose Fermenters (NLFs): Is there a Difference in Outcomes?

Presenter: Thomas Lodise

Poster #216: Association between Days to Initiate Appropriate Therapy and Hospital Length of Stay Among Adult Hospitalized Patients with Gram-negative Bloodstream Infections (GN-BSI)

Presenter: Thomas Lodise

Session title: HAI: MDRO – GNR Epidemiology, CRE

Poster #500: Prevalence of Extended Spectrum β-lactamase and Carbapenem-Resistant Gram-Negative Bacteria in Patients with Urinary Tract Infection and Urosepsis Admitted through U.S. Emergency Departments

Presenter: Sukhiit Takhar

Session title: HAI: MDRO – GNR Epidemiology, Acinetobacter

Poster #551: Burden of Illness in Carbapenem-resistant Acinetobacter baumannii Infections in US Hospitals (2014 to 2018)

Presenter: Jason Pogue

Session title: Novel Antimicrobials and Approaches Against Resistant Bugs

Poster #666: Efficacy and Safety of Cefiderocol According to Renal Impairment in Patients with Complicated Urinary Tract Infection (cUTI) in a Phase 2 Study

Presenter: Simon Portsmouth

Poster #679: In Vitro Activity of Cefiderocol (CFDC), a Novel Siderophore Cephalosporin, Against Difficult-to-Treat Resistant (DTR) Gram-negative Bacterial Pathogens from the Multi-national Sentinel Surveillance Study, SIDERO-WT (2014–2017)

Presenter: Christopher Longshaw

Poster #692: In Vitro Antibacterial Activity of Cefiderocol against a Multi-national Collection of Carbapenem-non-susceptible Gram-negative Bacteria from Respiratory Infections: SIDERO-WT-2014–2017

Presenter: Sean Nguyen

Poster #696: Cefiderocol Susceptibility Against Molecularly Characterized Carbapenemase-producing Gram-negative Bacteria in North America and Europe Between 2014 and 2017: SIDERO-WT-2014 to -2016 Studies

Presenter: Takafumi Sato

Poster #719: Cefiderocol Retains Anti-Biofilm Activity in MDR Gram-Negative Pathogens
Presenter: Christine Pybus

Poster #721: In Vitro Activity of Cefiderocol Against Gram-negative Clinical Isolates from New York City

Presenter: Zeb Khan

Poster #723: Synergistic Effect of Cefiderocol Combined With Other Antibiotics Against Cefiderocol High MIC Isolates From the Multi-national SIDERO-WT Studies

Presenter: Yoshinori Yamano

Poster #730: Cefiderocol for the Treatment of Achromobacter xylosoxidans Infections in Two Lung Transplant Patients with Cystic Fibrosis

Presenter: Nathaniel Warner

Poster #739: Prediction of Cefiderocol Pharmacokinetics and Probability of Target Attainment in Pediatric Subjects for Proposing Dose Regimens

Presenter: Takayuki Katsube

Date and time: October 4, 12:15 p.m.-1:30 p.m.

Location: Poster Hall at the Walter E. Washington Convention Center

Session title: Urinary Tract Infections

Poster #1458: Burden of Illness in Patients with Urinary Tract Infections with or without Bacteremia Caused by Carbapenem-resistant Gram-negative Pathogens in US Hospitals (2014 to 2018)

Presenter: Ryan Shields

Poster #1473: Structured Patient Interview in Complicated Urinary Tract Infections to Assess Clinical Outcomes Versus Investigator’s Evaluation in the APEKS-cUTI Study

Presenter: Simon Portsmouth

Session title: PK/PD & Susceptibility Testing

Poster #1544: Efficacy of Human-Simulated Cefiderocol Exposure Against Gram-Negative Bacteria in an Iron-Overloaded Murine Thigh Infection Model

Presenter: James Kidd

Poster #1553: Human-Simulated Pharmacokinetic Profiles of Cefiderocol and Meropenem are Conserved in Murine Models of Thigh Infection With or Without Iron Overload

Presenter: James Kidd

Date and time: October 5, 12:15 p.m.-1:30 p.m.

Location: Poster Hall at the Walter E. Washington Convention Center

Session title: Clinical Outcomes of Infections with Resistant Organisms

Poster #2275: Novel Therapeutic Options for the Treatment of Multi-Drug Resistant Achromobacter Respiratory Infections

Presenter: Sarah Minor

XOFLUZA

Date and time: October 4, 12:15 p.m.-1:30 p.m.

Location: Poster Hall at the Walter E. Washington Convention Center

Session title: PK/PD & Susceptibility Testing

Poster #1536: Population Pharmacokinetic Analysis of Baloxavir Marboxil, a Cap-dependent Endonuclease Inhibitor, in Adults and Adolescents and Exposure-Response Relationships in the Patients at High-Risk of Influenza Complications

Presenter: Hiroki Koshimichi

About Cefiderocol–An Investigational Antibiotic Agent

Cefiderocol is a parenteral siderophore cephalosporin with a novel mechanism for penetrating the outer cell membrane of Gram-negative pathogens including multidrug-resistant strains. 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.¹In 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-beta-lactamases.² These mechanisms allow cefiderocol to achieve higher concentrations in the periplasmic space where it can bind to receptors and inhibit cell wall synthesis in the bacterial cells.³ Data from multinational surveillance studies for cefiderocol 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).⁴ Cefiderocol has poor in vitro activity against Gram-positive or anaerobic bacteria. The clinical significance of in vitro data is unknown.

Shionogi submitted a New Drug Application to the U.S. Food and Drug Administration (FDA). Cefiderocol was designated as a Qualified Infectious Disease Product (QIDP) by the FDA with the assigned action date of November 14, 2019 under the Prescription Drug User-Fee Act (PDUFA). Additionally, Shionogi also submitted a marketing authorization application of cefiderocol to the European Medicines Agency and it was accepted in March 2019.⁵

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 P. aeruginosa, A. baumannii, and S. maltophilia, means there is a critical need for new, effective therapies.^{4, 6-9}There are an increasing number of Gram-negative pathogens resistant to multiple antibiotics, making them difficult to treat and resulting in high mortality rates.¹⁰ In the U.S., at least two million people are infected with antibiotic-resistant bacteria, and at least 23,000 people die as a result each year.¹¹ In the EU, about 25,000 patients die from an infection with the selected multidrug-resistant bacteria.¹²The 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.^6,11

About XOFLUZA™ (baloxavir marboxil)

XOFLUZA, discovered by Shionogi, has a novel mechanism of action that inhibits cap-dependent endonuclease in the polymerase acidic (PA) protein (in the United States Prescribing Information, this enzyme is stated as polymerase acidic endonuclease), an enzyme essential for viral replication. The regimen for XOFLUZA is one-oral dose to treat uncomplicated influenza, which is different from all currently available antiviral treatments. In non-clinical studies, XOFLUZA demonstrated an antiviral effect against a wide range of influenza viruses including oseltamivir-resistant strains and avian strains (H7N9, H5N1).^13-14 XOFLUZA was approved and is now available in Japan for the treatment of influenza Types A and B in adults and paediatric patients.¹⁵ In addition, XOFLUZA was approved in Taiwan on August 28, 2019, for the treatment of acute influenza Types A and B in patients aged 12 years of age and older.¹⁶

Shionogi and the Roche Group, which includes Genentech in the U.S., have a license and collaboration agreement to further develop and commercialize XOFLUZA globally. Under the terms of this agreement, Roche Group holds worldwide rights to XOFLUZA excluding Japan and Taiwan, which will be retained exclusively by Shionogi & Co., Ltd. XOFLUZA is currently available across the U.S. for the treatment of acute, uncomplicated influenza in people 12 years of age or older.¹⁷ The U.S. Food and Drug Administration (FDA) has accepted a supplemental NDA for XOFLUZA for the treatment of influenza in individuals at high-risk for influenza-related complications 12 years and older. The PDUFA date for an FDA decision is November 4, 2019.¹⁸ For more information, please refer to the XOFLUZA website.

Roche is now conducting a Phase III development program including children under the age of one year, and severely ill, hospitalized patients, as well as to assess the potential to reduce transmission of influenza from an infected person to healthy people. Shionogi is assessing the potential of XOFLUZA as a post-exposure prophylaxis treatment to prevent the spread of influenza in adults and children, and positive results were obtained in the Phase III study.¹⁹

About Influenza

Seasonal and pandemic influenza remain a major public health concern, and novel influenza drugs that will offer significant improvement over current therapy are urgently needed. Globally, seasonal epidemics result in three-to-five million cases of severe disease, millions of hospitalizations and up to 650,000 deaths every year.^20-24

About Shionogi

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 www.shionogi.co.jp/en. Shionogi Inc. is the U.S. subsidiary of Shionogi & Co., Ltd. based in N.J. For more information on Shionogi Inc., please visit https://www.shionogi.com/.

Forward-Looking Statements

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.

References

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