Sean Bergenheim and Tim Jackman scored for the Islanders, who have lost three in a row.
The Islanders took 13 of the game's first 16 shots and Bergenheim scored on No. 13 - taking a pass from Doug Weight and beating Biron for his 15th goal of the season at 14:06.
Lupul tied it up at 5:04 of the second period during Philadelphia's first power play. His wrist shot from the top of the right circle got past Yanis Danis.
The Flyers took a 2-1 lead on their second power play, as Knuble finished off a scramble in front of the net by putting the puck past Danis. Jackman tied the game at 15:23 on a shot that surprised Biron.
Gagne restored Philadelphia's lead 52 seconds later on a wrist shot.
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