I have never personally seen a randomized study with anywhere near 40k+ participants for any cardiology or cancer-related treatment. Recruitment for this vaccine trial is much easier than studies with specific conditions like heart attack, stroke, or cancers, simply due to their incidence rates. In cardiology, a 20k subject study is massive in scale.
All this to say that for the pivotal phase 3 trials submitted to FDA for approval, I would suppose almost all existing drugs had much fewer than 40k participants.
It looks like the initial approval of Lipitor was in the hundreds of patients. Now, statins were brand new and not used really broadly. Pfizer did a ton of follow up studies, but looking at the most current label.
The two biggest trials, ASCOT and CARDS, which measured improvements in mortality (needed to be big trials to measure any difference), they were ~10,000 and ~2,000 patients each.
So suffice to say, Lipitor, which is used in a massive population, has probably been tested, in clinical trials, on a total number of patients comparable to the Pfizer Covid vaccine trial. Obviously the duration of the Lipitor trials were much longer and there a massive body of clinical data from actual use, but it at least gives you some perspective on numbers.
All this to say that for the pivotal phase 3 trials submitted to FDA for approval, I would suppose almost all existing drugs had much fewer than 40k participants.