Officials say the fire started around 12:20 a.m. on the 6000 block of North 12th Street.
Companies responded to the fire in three minutes.
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When fire crews arrived, there was heavy smoke coming from the two-story home. Firefighters say conditions inside the home were challenging.
"When companies came on scene, they found heavy smoke conditions on the first floor and throughout the entire structure," said Assistant Chief Charles Walker, with the Philadelphia Fire Department.
Investigators say they didn't find any smoke alarms inside the house and no sirens were going off when they entered.
"They made an aggressive forcible entry at the front door and the companies encountered a lot of debris on the first floor," Walker said.
Fire crews pulled a 60-year-old woman from the house. She was taken to Albert Einstein Hospital with serious burns.
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A male victim was also found dead inside the house.
The cause of the fire is under investigation