Why are the run times so different?

There are several reasons:

In the US (& Canada), foreign-made films were often edited down by distributors, so they could fit in more cinema screenings in one day (more profits) or so they could accompany other films as the B-feature on a double bill.

Subsequently, they were often edited even further for television broadcast, especially once they entered the public domain, as happened with The Speckled Band.

As many of the reviews point out, this film has much to recommend it, from Massey's acting, to the pervading gothic gloom & somewhat expressionistic touches.

It would be wonderful if a better-preserved, more complete print than the currently-available 49 minute one were to surface.

Having watched this one several times, however, I think that an original running time of 66 minutes is perhaps more realistic.
In the absence of any completely excised sub-plots, it's hard to imagine that more than 25 or so minutes could be missing at present.

Astonishingly good film... But I saw the 49 minute version and it is full of awkward jumps. There are bits missing in the middle of scenes and there appear to be whole scenes missing. I am definitely hoping a longer cut turns up.