1343. Prophylactic Dosing of Baloxavir Acid Eliminates Mortality in Mice Lethal Influenza A Virus Infection Model
Session: Poster Abstract Session: Novel Agents
Friday, October 5, 2018
Room: S Poster Hall

Background: Baloxavir acid (BXA), an active form of orally available prodrug baloxavir marboxil (BXM, formerly S-033188), is a novel small molecule inhibitor of cap-dependent endonuclease (CEN) of influenza A and B virus, and was recently launched for the treatment of acute and uncomplicated influenza with single dosing of BXM (the trade name XOFLUZA™) in Japan in March 2018.  Here, we evaluated the prophylactic efficacy of BXA in mice lethally infected with influenza A virus.

Methods: T1/2 of BXA in human is more than 10-times longer than that in mice. Therefore, suspension of BXA was subcutaneously administered at 0.8 or 1.6 mg/kg in mice to maintain the plasma concentration of BXA as seen in humans, and then mice were intranasally inoculated with a lethal dose of A/PR/8/34 strain at 48, 72, or 96 hours after the administration of BXA.  Survival time and body weight change were then monitored through a 28-day period after virus infection.  Mice were euthanized and regarded as dead if their body weights were lower than 70% of the initial body weights according to humane endpoints.

Results: Single dosing of BXA (1.6 mg/kg) completely eliminated mortality in mice, when the mice were administrated the drug at 48, 72 or 96 hours before virus infection (Figure 1).  BXA treatment also significantly prevented body weight loss, consistent with the prolonged survival.

Conclusion: Prophylactic dosing of BXA exhibited significant protective efficacy against mortality and body weight loss in mice following a lethal infection with influenza A virus.  The significant prophylactic efficacy observed in our mouse model suggests the potential utility of BXM for the prophylaxis of influenza in human.

Shinya Shano, MS1, Keita Fukao, MS1, Takeshi Noshi, MS1, Kenji Sato, MS1, Masashi Sakuramoto, MS1, Kaoru Baba, AS2, Takao Shishido, PhD1 and Akira Naito, Ph. D.1, (1)Shionogi & Co., Ltd., Osaka, Japan, (2)Shionogi TechnoAdvance Research & Co., Ltd., Osaka, Japan

Disclosures:

S. Shano, Shionogi & Co., Ltd.: Employee , Salary .

K. Fukao, Shionogi & Co., Ltd.: Employee , Salary .

T. Noshi, Shionogi & Co., Ltd.: Employee , Salary .

K. Sato, Shionogi & Co., Ltd.: Employee , Salary .

M. Sakuramoto, Shionogi & Co., Ltd.: Employee , Salary .

K. Baba, Shionogi TechnoAdvance Research & Co., Ltd.: Employee , Salary .

T. Shishido, Shionogi & Co., Ltd.: Employee , Salary .

A. Naito, Shionogi & Co., Ltd.: Employee , Salary .

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