A colleague and I were talking the other day about the (long) list of drugs that have been left for dead at some point during their development. There are some famous cases – Lipitor, for example, which wasn’t thought by many at Warner-Lambert to have a business case worth even taking into the clinic. But these things are all over the place.
One that I know about was Claritin (loratadine). Schering-Plough worked on nonsedating antihistamines for a while, without too much success, and the whole program was eventually killed. The head of research at the time stated flatly: “There are no nonsedating antihistamines”. Of course, when the first one (Seldane) came on the market, that made everyone rethink a bit. In the interim, one of the chemists had continued making compounds, despite several (increasingly testy) warnings to stop.
As it turned out, he (Frank Villani) and one of his associates (Charlie Magatti) had made loratadine itself, the nonsedating antihistamine which helped to pay everyone’s salary at Schering-Plough through the 1990s. But by the time that was worked out, Villani himself had been eased out the door (or not eased while on his way out, depending on who you talk to), in good part due to his continued work on the compounds. That head of research, to his credit, actually referred ruefully later on to his own “no nonsedating antihistamines” comment – there are plenty of other people who would have just Never Said Such a Thing At All in that position.
You can find a lot of other examples, going back a long way. Many of these are medical and marketing arguments: ACE inhibitors weren’t necessarily going to be of that much use for hypertension (how many people had high blood pressure because of problems with their renin-angiotensin system anyway?) And the K/H ATPase compounds weren’t going to be of much use for acid reflux, because the H2 antagonists had the market covered (Prilosec and its progeny managed to carve out a little market share for themselves, though). The Lipitor-won’t-make-any-money mistake falls squarely into this category.
My theory is that it’s always possible to find a list of plausible reasons why a given project, or a given drug candidate, won’t work. Finding those things is (comparatively speaking) the easy part. The hard part is working out which of those things you’re wrong about, because you’re sure to be wrong about some of them. (Of course, thinking about this stuff makes you start to wonder about the drugs that never quite made it, but would have done well if they had. Most experienced development people have a list of might-have-beens that they still wonder about, but some of those would surely have also blown up disastrously even later in the process, taking even more money with them).
Further that’ll-never-work examples are welcome in the comments. I know there must be plenty of them out there. . .