So, number 1 - route stability. Fundamentally, trade benefits everyone, during the first period of peace, SOMEONE will notice the benefits, and try and capitalize upon it - and building an army built on that wealth to take over their region - making the trade viable at least through their territory. (For example someone in Kashgar stabilizing the Taklamakan Desert, or Samarkand stabilizing Central Asia.
number 2 - distances too long - fundamentally this requires the non-use of donkeys, horses, or the development of a "This isn't worth the trip" psyche. Now in reality almost nobody travelled the length of the Silk Road - they traded from stop to stop, increasing the prices as they go. Could this lead to prices being too exorbitant at the far end? Maybe, but they were already about as high as they could get. In which case, there may be less trade.
Personally, you're more likely to achieve this with a horse plague, or the extinction of the silkworm, perhaps preferred as food. Or, the early propagation of the silkworm and mulberry tree over the Indian Ocean - rendering the Silk Road useless as everyone can grow Silk (or many can, Siberia may have issues

)
If the Silk Route never really existed? I don't know - it is the natural response to supply and demand between civilisations, and it didn't just trade silk. I guess we're looking at a world without the major use of pack animals - which could mean the lack of the use of cavalry, making infantry the primary force in war.
So no Mongol Invasions/Huns, etc - but also no horse-shows, which is sad.
Frankly, I'm not sure it is plausible without making Silk commonplace to end the "Silk Route", but the routes would still be in use, regardless.