A couple of potential problems if this is meant as a major motion picture--
Would enough of the general public be willing to go to such a film to justify the cost? Fans might go see it, but what about Joe Blow from Kokomo?
Your box office stars would be unrecognizable under the heavy makeup. Planet of the Apes pulled it off, but a human character was the focal point.
I say yes. What's important is the execution, not the details. Big names are not important, recognizablity of the actors is not important. Otherwise original films with unknown actors would never be successful, and there are many many successful examples. Big Boo already mentioned Disney films, where there are no humans to see. And they are successful as well. Lord of the Rings, Apocalypto and Inglorious Basterds have shown that you can do huge chunks of the film in foreign language with subtitles.
Seriously, don't buy into that "general audience is stupid" sillyness. It's absolutely wrong. When a film fails, it's because of the overall impression, not because of "oh, there were no known actors" or "oh, I couldn't see his face" or "oh, I don't know Klingons" or "oh, I don't know the language".