Some aircraft have an Emergency Descent autopilot mode when cabin altitude climbs well above 8000 feet that turns the aircraft 90 degrees (to get off airway and bring ATC attention) and auto descends to 12,000 feet or so. During the descent their groundspeed would be lowered.
But if the crew was incapacitated and never recovered the a/c should just fly the new heading at 12,000 feet until fuel exhaustion.
Perhaps a fuselage failure initiated emergency descent mode and incapacitated the crew, followed a few minutes later by worsening damage sufficient to depart controlled flight?