Here are the reasons I've seen:

Difficulty learning the FMS.
Not current going into training and falling behind the curve a bit as a result.
Getting sick and falling behind.
Poor sim partner.
Poor instructor or one I know many who failed because of, an instructor with a chip on their shoulder looking to wash people out.
Entitlement attitude although I've only seen that in one occasion.
Lack of instrument skills.

I think often it's more than one reason. Sort of like an accident chain. Break one of those reasons and the failure doesn't occur. It's not like everyone that passes, sails through without difficulty.