The $2.5B number (and numbers around that mark) is the cost it takes to bring a single successful drug to marketwhen you consider cost of capital (i.e. how much you could earn if you put the money towards a different project) and the average costs of the failed drug projects in a company’s pipeline. See the methods section of https://jamanetwork.com/journals/jama/fullarticle/2762311 up to the section on sensitivity analysis. It is NOT a measure of the raw costs of drug development.

It’s more a measure of “how much revenue does a drug project need to generate to be worth investing in when we consider how many other projects will fall” than “how much would it theoretically cost to bring drug X through preclinical development, clinical trials, etc.” Drug X would need to generate more sales than its direct costs alone for the pharmaceutical company to turn a profit because it needs to also pay for an assumed amount of other failed projects.