Mass Effect 3 is no secret; BioWare's said for some time this is a trilogy. But we can expect that that sequel will be the final chapter - to this story arc, anyway.
Shacknews reports that Casey Hudson, the series' project director, told a press event in Edmonton that, "'Mass Effect 3' will be easier because we don't have to worry about the continuity into the next one."
There's no way BioWare will walk away from a money-printing IP like this, even after three titles, so it invites speculation on just what exactly they'll do with this universe they've built after Mass Effect 3. A prequel might be enticing, but you'd also have the whole "in what order do I play these" debate for people just coming to the series.