This is a good history of Keytruda, the Merck immuno-oncology blockbuster, from David Shaywitz. Most big drugs have a tangled history, and this one is certainly not going to break tradition. As witness:
It was discovered accidentally, by biotech scientists looking for drugs that would tamp down the immune response in patients with autoimmune disease, and would stimulate, not block, PD1. Even after a potent PD1 inhibitor was identified and recognized as a potential cancer drug, the research program had to fight for funding through two mergers and acquisitions. After the program finally wound up at Merck, in 2009, it was considered such a low priority that it was shut down and placed on the out-license list. A term sheet (valuing the program at next to nothing) was reportedly in place, but pulled at the last minute, as promising results from competitor Bristol-Myers Squibb (BMS) motivated a reconsideration of the mechanism.
I remember telling one group leader at a former company, who was running another very odd and unexpected project, that if I were ever sitting in the audience at some dinner where he was getting a plaque and an award, I would throw my baked potato at him if he used the phrase “As we expected. . .” And he agreed that he would deserve some incoming spuds if that happened. In the case of Keytruda, the story goes back to 2003, and back not to Merck, and not to Schering-Plough, but to Organon, the long-gone drug division of Akzo Nobel. The story does not, at least at first, cover Merck with glory, although once they got moving, they did an excellent job. This is far from the only drug involved in a merger or takeover (in this case, two) that turned out to be much more important than the ostensible reason for the whole deal (which tells you something about our ability to do scientific and commercial forecasting).
It’s as much the story, though, of Bristol-Myers Squibb letting an opportunity get away from them with their own competing antibody, Opdivo, which had years of head start. As the article shows, even up until early last year, Merck looked like an also-ran, but Roger Perlmutter’s decision to resource Keytruda with everything possible turned out to be the right one. (Needless to say, if something unexpected had gone wrong, he would have surely been out the door, and presumably would have had plenty of company, too). But Keytruda really did work, the clinical decisions really were the right ones, and spending all that money and effort really has turned out to be the right decision. But there’s a lot of luck involved. If Merck had tried head and neck cancer patients earlier, for example, they would have run into trouble, since the antibody failed pretty conclusively in a recent trial. You can argue that that one was always going to be further down the list, but no one expected the numbers to be as bad as they were.
No, time and chance happeneth to them all. The Keytruda story is certainly about persistence, about risk-taking, and about a huge amount of hard work and tough decision-making. But while those are necessary, they’re not quite sufficient. No one likes to think about that, and it’s certainly a lot easier, in the wake of a success, to imagine that it was all due to clear-eyed foresight. But that’s almost never the case. Was Merck good, or were they lucky? They were both. And good for them.