The defense has 5 seconds to react to this (even though the offense has been getting this package ready on their sideline for 2 or 3 plays). Of course, they're caught flat-footed—that's hardly enough time to think of a good counter-substitution, much less call those names, have those players sprint into position, and get their replacements off the field.

Advantage would be entirely in favor of the offense, who could:

• Quickly get set so as to snap the ball and get a free play/5 yards if the defense is still substituting
• Take a leisurely 10 seconds to get set, check the read on the sideline, and exploit the defensive unit on the field 
• Take advantage of near/far hashes to get advantageous mismatches (every time the defense switches to a set with more DBs, the offense could complete a pass to the hash near their sideline, rush a heavy set on, and then run against a light defense—too far for a heavy defensive set to sprint into position, especially since they have further to run)