There's a good chance that Isaac will be added to Project M along with the other characters who will never be playable in an actual Smash Bros game.
If they keep making Smash games, Sakurai will have to look at these characters again. Especially if they go more and more into only using a few IPs.
If a new person makes Smash, hopefully they'll be more inclined to focus on heavy and reasonable fan request rather than constantly being tempted to add "interesting" novelty characters. I think with Sakurai it will only get worse.