9/6/2018 Baloxavir Marboxil Phase II and III Studies for the Treatment of Influenza Published in the New England Journal of Medicine - Shionogi In…
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Baloxavir Marboxil Phase II and III Studies for the Treatment of In uenza Published in the New England Journal of Medicine
Sep. 6, 2018
OSAKA, Japan & FLORHAM PARK, N.J.–(BUSINESS WIRE (http://www.businesswire.com/))– Shionogi & Co., Ltd. (Head O ce: Osaka; President & CEO: Isao Teshirogi, Ph.D.; hereafter “Shionogi”) today announced the positive results from Phase II and III
studies of baloxavir marboxil for the treatment of in uenza in otherwise-healthy patients have been published in the New England Journal of Medicine (NEJM) in the September 6, 2018 issue.1 Baloxavir marboxil was discovered by Shionogi and has a novel mechanism of action that inhibits viral cap-dependent endonuclease.
In the Phase II study conducted in adults in Japan, baloxavir marboxil demonstrated a reduction in time to alleviation of symptoms and in in uenza virus titers compared with the placebo.2, 3, 4 In the global Phase III study (CAPSTONE-1) in patients
12 years of age and older, baloxavir marboxil reduced time to alleviations of symptoms (TTAS) compared with the placebo. On the other hand, there was no statistical di erence in TTAS between baloxavir marboxil and oseltamivir. Of note, baloxavir
marboxil demonstrated more rapid declines in infectious virus titers compared with both the placebo and oseltamivir. Regarding safety, baloxavir marboxil was well tolerated with a numerically lower overall incidence of adverse events compared
with both the placebo and oseltamivir.5, 6, 7
“In addition to its favorable safety and pharmacokinetic pro le enabling single dose oral therapy in uncomplicated in uenza, baloxavir marboxil’s antiviral potency o ers promise of potentially reducing complications and transmission of the virus to
others and in treating more serious forms of in uenza illness. It also addresses an important unmet medical need in inhibiting in uenza viruses that are resistant to currently available agents,” said Frederick G. Hayden, M.D., Stuart S. Richardson
Professor Emeritus of Clinical Virology and Professor Emeritus of Medicine, University of Virginia School of Medicine, the lead author of the published paper.
A timeline of important events in 2018 are as follows:
• February 23: Baloxavir marboxil was approved in Japan. Baloxavir marboxil is now available in Japan under the brand name ® XOFLUZA for the treatment of in uenza Types A and B in adults and pediatric patients.8
• April 24: Shionogi submitted a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for the treatment of acute uncomplicated in uenza in patients 12 years of age and older in collaboration with F. Ho mann-La
Roche Ltd. (hereafter “Roche”). On June 26, the FDA accepted the NDA and granted Priority Review. The Prescription Drug User Fee Act (PDUFA) date for an FDA decision is December 24, 2018.9
• June 29: Shionogi submitted a NDA for baloxavir marboxil in Taiwan for the treatment of in uenza in patients 12 years of
age and older.10
• July 17: Shionogi announced positive top-line results of CAPSTONE-2, a Phase III study in patients at high risk for in uenza- related complications. The results from the CAPSTONE-2 study will be presented at upcoming medical meetings.11
• September 6: The NEJM published the results of Phase II and Phase III studies of baloxavir marboxil for the treatment of in uenza in otherwise-healthy patients.1
https://www.shionogi.com/baloxavir-marboxil-phase-ii-and-iii-studies-for-the-treatment-of-influenza-published-in-the-new-england-journal-of-medicine/ 1/5 9/6/2018 Shionogi’sBaloxavir research Marboxil and Phase development II and III e orts Studies target for the infectious Treatment diseases of Influenza as one Published of its priority in the New areas, England and Shionogi Journal hasof Medicine positioned - Shionogi In… “protecting people from the threat of infectious diseases” as one of its core social missions. Shionogi strives constantly to bring forth innovative drugs for the treatment of infectious diseases, to protect the health of many patients we serve.
About Baloxavir Marboxil
Baloxavir marboxil, discovered and developed by Shionogi, has a novel mechanism of action that inhibits cap-dependent endonuclease, an essential enzyme for viral replication. The regimen for baloxavir marboxil is a single-oral dose to treat
uncomplicated in uenza, which is di erent from most currently available antiviral treatments. In non-clinical studies, baloxavir marboxil demonstrated an antiviral e ect against a wide range of in uenza viruses including oseltamivir-resistant strains and avian strains (H7N9, H5N1).12, 13, 14
Shionogi and the Roche Group which includes Genentech in the U.S. are in a license and collaboration agreement to further develop and commercialize baloxavir marboxil globally. Under the terms of this agreement, the Roche Group holds worldwide rights to baloxavir marboxil excluding Japan and Taiwan where the rights are retained exclusively by Shionogi. Roche will further investigate baloxavir marboxil in a global Phase III development program including pediatric and severely ill
hospitalized populations with in uenza. Shionogi will conduct a post-exposure Phase III prophylaxis study in Japan in the 2018/2019 u season.
About In uenza
Seasonal and pandemic in uenza remain a major public health concern, and novel in uenza drugs that will o er signi cant improvement over current therapy are urgently needed. Globally, annual epidemics result in 3 to 5 million cases of severe disease, millions of hospitalizations and up to 650,000 deaths worldwide.15, 16, 17, 18, 19
About Shionogi
Shionogi & Co., Ltd. is a Japanese major research-driven pharmaceutical company dedicated to bringing bene ts to patients based on its corporate philosophy of “supplying the best possible medicine to protect the health and wellbeing of the patients we serve.” Shionogi Inc., the U.S. based subsidiary of Shionogi & Co., Ltd., continues this focus on the development and commercialization of high quality medicines that protect the health and well-being 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., please visit www.shionogi.co.jp/en (http://cts.businesswire.com/ct/CT? id=smartlink&url=http%3A%2F%2Fwww.shionogi.co.jp%2Fen%2F&esheet=51862596&newsitemid=20180905006055&lan=en-
US&anchor=www.shionogi.co.jp%2Fen&index=1&md5=6800056d6b10615bba93f43426909048). For more information on Shionogi Inc., please visit www.shionogi.com (http://cts.businesswire.com/ct/CT? id=smartlink&url=http%3A%2F%2Fwww.shionogi.com&esheet=51862596&newsitemid=20180905006055&lan=en- US&anchor=www.shionogi.com&index=2&md5=4bea2840 fdbe494aad46232d68e46c).
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 di er 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 e cacy; 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
https://www.shionogi.com/baloxavir-marboxil-phase-ii-and-iii-studies-for-the-treatment-of-influenza-published-in-the-new-england-journal-of-medicine/ 2/5 9/6/2018 productionBaloxavir capacity Marboxil to meet Phase demand, II and unavailabilityIII Studies for ofthe raw Treatment materials of andInfluenza entry ofPublished competitive in the products. New England The company Journal disclaimsof Medicine any - Shionogi In… intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or
otherwise.
Reference:
1. Frederick G. Hayden et al. Baloxavir Marboxil for Uncomplicated In uenza in Adults and Adolescents. N Engl J Med 2018 Sep 6; 379:913-923. https://www.nejm.org/doi/full/10.1056/NEJMoa1716197?query=featured_home (http://cts.businesswire.com/ct/CT? id=smartlink&url=https%3A%2F%2Fwww.nejm.org%2Fdoi%2Ffull%2F10.1056%2FNEJMoa1716197%3Fquery%3Dfeatured_home&esheet=51862
US&anchor=https%3A%2F%2Fwww.nejm.org%2Fdoi%2Ffull%2F10.1056%2FNEJMoa1716197%3Fquery%3Dfeatured_home&index=3&md5=3c1
2. Press release on August 29, 2016 (http://cts.businesswire.com/ct/CT? id=smartlink&url=http%3A%2F%2Fwww.shionogi.co.jp%2Fen%2Fcompany%2Fnews%2F2016%2Fpmrltj0000002zx1-
att%2Fe160829.pdf&esheet=51862596&newsitemid=20180905006055&lan=en- US&anchor=Press+release+on+August+29%2C+2016&index=4&md5=61b424982c60a787ddf916b27f41bfde)
Shionogi Presents Results from a Phase 2 Proof-of-Concept Clinical Trial and Non-Clinical Studies of S-033188, a Novel Cap- Dependent Endonuclease Inhibitor for Treatment of In uenza – Oral Presentation and Posters Presented at Options IX –
3. Press release on December 1, 2016 (http://cts.businesswire.com/ct/CT? id=smartlink&url=http%3A%2F%2Fwww.shionogi.co.jp%2Fen%2Fcompany%2Fnews%2F2016%2Fpmrltj00000034lx- att%2Fe161201.pdf&esheet=51862596&newsitemid=20180905006055&lan=en-
US&anchor=Press+release+on+December+1%2C+2016&index=5&md5=25b24c837edabb0de6241d378194ec86)
Secondary Endpoint Data for S-033188, a Novel Cap-Dependent Endonuclease Inhibitor for Treatment of In uenza, Support Favorable Primary Endpoint Data Previously Released – Oral Presentation Presented at APCCMI –
4. Press release on April 25, 2017 (http://cts.businesswire.com/ct/CT? id=smartlink&url=http%3A%2F%2Fwww.shionogi.co.jp%2Fen%2Fcompany%2Fnews%2F2017%2Fpmrltj0000003byn- att%2Fe170425_1.pdf&esheet=51862596&newsitemid=20180905006055&lan=en-
US&anchor=Press+release+on+April+25%2C+2017&index=6&md5=8a4c462b14384bd014c80b8612622c01)
Shionogi Presents Results of the First Clinical E cacy Trial and In Vitro Data on Ce derocol (S-649266), a Siderophore Cephalosporin
5. Press release on July 24, 2017 (http://cts.businesswire.com/ct/CT? id=smartlink&url=http%3A%2F%2Fwww.shionogi.co.jp%2Fen%2Fcompany%2Fnews%2F2017%2Fpmrltj0000003ft2-
att%2Fe170724.pdf&esheet=51862596&newsitemid=20180905006055&lan=en- US&anchor=Press+release+on+July+24%2C+2017&index=7&md5=f5e9e9daf7de1e4602a3 a2494dc29d)
Shionogi Announces Positive Top-Line Results for S-033188 Phase 3 Study (CAPSTONE-1) in Otherwise Healthy In uenza
Patients
6. Press release on September 13, 2017 (http://cts.businesswire.com/ct/CT?
id=smartlink&url=http%3A%2F%2Fwww.shionogi.co.jp%2Fen%2Fcompany%2Fnews%2F2017%2Fpmrltj0000003hmx-
att%2Fe170914.pdf&esheet=51862596&newsitemid=20180905006055&lan=en- US&anchor=Press+release+on+September+13%2C+2017&index=8&md5=56af76a3f11ede2dca72ca8155777368)
S-033188 Phase 3 CAPSTONE-1 Study Results for Treatment of In uenza Presented at the European Scienti c Working Group
on In uenza Conference
https://www.shionogi.com/baloxavir-marboxil-phase-ii-and-iii-studies-for-the-treatment-of-influenza-published-in-the-new-england-journal-of-medicine/ 3/5 9/6/2018 7. PressBaloxavir release Marboxil on October Phase 5, II2017 and (http://cts.businesswire.com/ct/CT?III Studies for the Treatment of Influenza Published in the New England Journal of Medicine - Shionogi In… id=smartlink&url=http%3A%2F%2Fwww.shionogi.co.jp%2Fen%2Fcompany%2Fnews%2F2017%2Fpmrltj0000003iol-
att%2Fe171006.pdf&esheet=51862596&newsitemid=20180905006055&lan=en-
US&anchor=Press+release+on+October+5%2C+2017&index=9&md5=291f64bf71ba2fe153298b163f161298)
Shionogi to Present S-033188 Phase 3 Capstone-1 Study Results for Treatment of In uenza at IDWeek 2017
8. Press release on March 14, 2018 (http://cts.businesswire.com/ct/CT?
id=smartlink&url=http%3A%2F%2Fwww.shionogi.co.jp%2Fen%2Fcompany%2Fnews%2F2018%2Fpmrltj0000003oid- att%2Fe180314.pdf&esheet=51862596&newsitemid=20180905006055&lan=en-
US&anchor=Press+release+on+March+14%2C+2018&index=10&md5=2a0efd0799b0c16987a724f99bce2faf)
XOFLUZA (Baloxavir Marboxil) Tablets 10mg/20mg for the Treatment of In uenza Types A and B launched in Japan
9. Press release on June 26, 2018 (http://cts.businesswire.com/ct/CT? id=smartlink&url=http%3A%2F%2Fwww.shionogi.co.jp%2Fen%2Fcompany%2Fnews%2F2018%2Fpmrltj0000003v8a-
att%2Fe_180626.pdf&esheet=51862596&newsitemid=20180905006055&lan=en- US&anchor=Press+release+on+June+26%2C+2018&index=11&md5=2e95fb530b24e4cbe67b17ccdf9bce0d)
FDA Accepts Baloxavir Marboxil New Drug Application and Grants Priority Review for the Treatment of In uenza
10. Press release on July 2, 2018 (http://cts.businesswire.com/ct/CT?
id=smartlink&url=http%3A%2F%2Fwww.shionogi.co.jp%2Fen%2Fcompany%2Fnews%2F2018%2Fpmrltj0000003vit- att%2Fe_180702.pdf&esheet=51862596&newsitemid=20180905006055&lan=en-
US&anchor=Press+release+on+July+2%2C+2018&index=12&md5=e2dbe5e0b3b2ec96e3fd0e1761e 244)
Shionogi Filed for the New Drug Application of Baloxavir Marboxil in Taiwan for the Treatment of In uenza
11. Press release on July 17, 2018 (http://cts.businesswire.com/ct/CT?
id=smartlink&url=http%3A%2F%2Fwww.shionogi.co.jp%2Fen%2Fcompany%2Fnews%2F2018%2Fpmrltj0000003w9m-
att%2Fe_180717.pdf&esheet=51862596&newsitemid=20180905006055&lan=en- US&anchor=Press+release+on+July+17%2C+2018&index=13&md5=c47b6b4be5babe53c5da9370f3082fcf)
Shionogi Announces Positive Top-Line Results for Baloxavir Marboxil Phase III Study (CAPSTONE-2) in Individuals at High Risk
for In uenza-Related Complications
12. T. Noshi et al. S-033447/S-033188, a Novel Small Molecule Inhibitor of Cap-dependent Endonuclease of In uenza A and B
Virus: In Vitro Antiviral Activity against Laboratory Strains of In uenza A and B Virus in Madin-Darby Canine Kidney Cells. Poster
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US&anchor=https%3A%2F%2Fwww.cdc.gov%2F u%2Fabout%2Fdisease%2F2015- 16.htm&index=16&md5=132365a90a6feddd505f824eb09c6248) CDC website, Estimated In uenza Illnesses, Medical Visits,
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