The 225-issue Nikkei Stock Average finished 236.16 points, or 0.83 percent, higher from Wednesday at 28,798.37.
The broader Topix index of all First Section issues on the Tokyo Stock Exchange closed 17.92 points, or 0.91 percent, higher at 1,989.43.
Trading volume on the main section decreased to 813.50 million shares from Wednesday's 874.92 million shares.
Tokyo stocks opened high from the outset but moved in a narrow range in the morning. Despite the low trading volume, stocks extended gains in the afternoon as market sentiment was lifted after U.S. regulators approved the emergency use of the first oral COVID-19 drug, developed by Pfizer Inc., brokers said.
Masahiro Ichikawa, the chief market strategist at Sumitomo Mitsui DS Asset Management Co., said, "The authorization of the new drug lifted expectations that its widespread use may prevent future lockdowns and limit potential restrictions in movement despite the recent surge in COVID-19 cases."
However, he added that gains were capped due to the community transmission of the Omicron variant in Osaka, as investors shifted attention to how the government will try to prevent the spread.
Japan's Osaka Prefecture on Wednesday reported three cases infected with the new variant through unknown routes. With no history of overseas travel, the three family members were admitted to a hospital after developing mild symptoms such as fever between Saturday and Monday, according to the local government.
By the close of play, mining, air transportation, and marine transportation companies headed the uptrend of the day. Advancing issues outnumbered declining ones 1,421 to 646 on the First Section, while 117 finished unchanged.
Tokyu Fudosan Holdings rose 4.4 percent after the real estate firm on Wednesday said that its subsidiary and variety store operator Tokyu Hands Inc. is to be bought by DIY store giant Cainz Corp.
Bucking the uptrend, pharmaceutical company Eisai dropped 9.1 percent after Japan's health ministry refused to approve its new Alzheimer's disease drug jointly developed with U.S. pharmaceutical giant Biogen Inc. due to lack of data.
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