In my experience, replies are usually tracked as part of the business process itself because replies reveal the sales status of the lead.
So, if you're sending emails to "New" leads and one of them replies, the assumption is that whoever is fielding the reply should be logging into the CRM to update the lead from "New" to now "Qualified" or "Nurture" or "Disqualified" or some equivalent.
And it's based on this "Lead Status" that you can then send your 2nd email. In other words, send the 2nd email to the leads that are still "New."
Hope that helps!