The suspects in a possible stolen car fled at high speeds from the Pacoima area onto the 118 Freeway and then southbound on the 405.
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The fleeing vehicle clipped another car and spun out on the southbound 405, crashing into a pole and leaving mangled wreckage on the side of the freeway near the Sherman Way exit.
Three people were thrown from the vehicle onto the side of the freeway. They looked to have sustained major injuries.
Paramedics were on scene treating the injuries.
High-speed chase ends in violent crash on 405 in Van Nuys
Five suspects were involved. The Los Angeles Fire Department said three of them were teenagers.
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Three suspects were hospitalized, while two tried to flee the scene on foot and were later taken into custody.
The southbound 405 was shut down at the Victory Boulevard exit and reopened at about 2:40 a.m. Friday, according to the California Highway Patrol.
The other car that was struck on the freeway spun around but then was able to pull safely over to the side of the road. It did not appear the occupants sustained major injuries.
The driver who was clipped is OK and says he was driving home from work when it happened, and he immediately rushed to help.
"They hit the pole and they ejected out of the car," said the driver Vikram Samra. "We immediately got out and ran toward them. We called the police as fast as we could, but they were here within minutes."