Can Prism fit models defined by a differential equation.

Starting with Prism 6, but Prism can fit a model defined by a differential equation. You must write an equation that defines Y' (same as dY/dX) as a function of Y and parameters.  Here is the page in Prism 6 help that explains how it works. 

Note however that Prism cannot fit models where intermediate variables are defined by differentital equations. It cann't fit a system of differential equations, only an equation that defines Y'. Two programs (not associated with GraphPad) that fit models defined by a system of differential equations (including intermediate variables) are  Berkeley Madonna and Scientist.