The Ford E series platform is generally pretty reliable and predictable. Major problems are rare (but do exist occasionally, of course). There are a few common problems that may need taking care of; brake calipers tend to get somewhat sticky from non-use not infrequently, for instance, and often the alignment ought to be improved from how it's delivered (mostly increasing the caster to the upper end of the allowable range). For the most part, though, the chassis if given reasonable care is not too likely to give significant trouble.
I wouldn't be overly concerned about the manufacturer having gone out of business as most components come from the same few other companies--the appliances, windows, many standard trim pieces, etc. Then, too, even if the maker is still in business it's no guarantee that they would have any unique parts still available.
For a used motorhome, the initial build is of some importance, but the quality of the maintenance and care the previous owner(s) gave is, in my opinion, of rather greater importance.
I have one with the four speed transmission. It works fine, but more gears would definitely be an improvement; the jumps when upshifting or downshifting are anything but subtle. 4th and 5th gear on the five speed are basically the same as 3rd and 4th on the four speed, so on the highway it has similar jumps when shifting; however, the control logic is somewhat improved. The six speed is definitely preferable to either one.
There is one recall on many years of the E series (and many other Ford trucks) for the cruise control brake switch. If that hasn't been done and is applicable, get it done. They had a tendency to, on rare occasions, short out and catch fire, and that could happen at any time as the circuit is live even with the ignition off.