The road is closed and there are no detours in place.
Police advise motorists to check the New Zealand Transport Agency website for further updates.
The police serious crash unit is on its way from Dunedin. A crash investigation will be carried out.
St John ambulance spokesman Ian Henderson said two patients with serious injuries were being flown by rescue helicopter to Dunedin Hospital.
Two others with moderate injuries were being flown in a second rescue helicopter to Christchurch Hospital with moderate to serious injuries.
Mr Henderson said a fifth patient with minor to moderate injuries was being taken by road ambulance to Timaru Hospital.