I said, in reference to the work others have done in analyzing Fifth Head, that "there doesn't seem to be a level at which the book can be read purely as entertainment." I should have said, more clearly, that the book's analysts don't seem to recognize such a level. (I may be wrong about that.)
If it is indeed true that the book can't be enjoyed without the help of scholars, then Wolfe has failed as an artist. But I don't think he has. I think he meant for the book to be read as a deeply mysterious story with no obvious answers to its many mysteries. That's how one experiences the extremely alien quality of St. Anne and St. Croix. (Note the contrast between the common place names and the uncommon places they designate. Our own world can be like that.)
This is not to say that the mysteries in Fifth Head, like those in any top-notch mystery story, aren't carefully constructed by the author, or that these mysteries can't be (at least partially) solved by someone willing to do a good deal of work.
So it all depends on whether you're the type of reader who can enjoy a deeply mysterious story with no obvious answers to its many mysteries. (Sharing the author's Catholic / Christian view of life, the universe, and everything probably helps in this regard.) Or whether you're the type of reader who simply must know all the answers.
Personally, I think over-analysis ruins the enjoyment of stories by Catholic / Christian authors like C.S. Lewis, J.R.R. Tolkein, Charles Williams, Henri Bosco, Zenna Henderson, R.A. Lafferty, and Gene Wolfe. These authors all have a deep respect for Mystery with a capital "M."