I found Prion really difficult on Mega Brutal. I did it once, couldn't remember how, and tried loads of different strategies before I found one that worked - twice. Please note, I play on my tablet, I don't know how well this strategy will work on Xbox One or other devices.
Here's how I did it:
I got Coma and Paralysis to slow the cure down.
I chucked everything I could at it, anything that looked likely to slow it down.
Finally, the cure stopped increasing at 94% and I was home and dry, exterminating humankind with a total of 15900 points.