The InVivo Blog has a good article on a controversy in the blood-thinning market. Plavix (clopidogrel) has a very strong share of that, of course, but since Effient (prasugrel) was finally approved, Lilly (LLY) and Dai-Ichii are looking to take as much of that market as they can. And one opening might be that not everyone responds similarly to Plavix.
In some cases, that's because there are some drug-drug interactions, a problem the FDA has recently addressed. The proton pump inhibitors, especially, are metabolized through the CYP2C19 pathway. That's a problem, since that enzyme is needed to convert clopidogrel into its active form (Plavix, as it comes out of the pill, is a prodrug - its thiophene ring needs to get torn open). This sort of thing has been seen many times before - it's one of the many headaches that you can endure in drug development as you profile the metabolizing pathways for your drug candidate and compare them to the other compounds your patient population might be taking. There are some combinations that just will not work (several involving CYP3A4, which is often the first one you test for), and it looks like we can add Plavix/2C19 to the list.
But the population genetics of the 2C19 enzyme are rather heterogeneous. About a third of the patients taking Plavix have a less-active form of the enzyme to start with, and they might not respond as robustly to the drug. The FDA has emphasized this effect in its latest public health warning. That's an opportunity for Effient, since it doesn't go through that metabolic route.
The In Vivo people point out, though, that this story isn't being driven by the usual players. It's not the FDA that's pushed to find this out, and it's not even Eli Lilly. It's Medco (MHS) and Aetna (AET). They studied their insurance claims data to see if the numbers supported the proton pump inhibitor/Plavix interaction, found that they did, and publicized their findings - and that led to an actual observational trial from Bristol-Myers Squibb (BMY) and Sanofi (SNY), which confirmed the problem. Now Medco is going further, and is actually running its own observational study comparing Plavix and Effient. Their theory is that the efficacy that Lilly showed compared to Plavix was driven by the (deliberate, one assumes) inclusion of a high number of poor metabolizers.
Medco is getting ready for generic Plavix, and trying to keep its costs down by making the case that the drug will do the job just fine for most patients. They could, on the other hand, end up making the case for Effient in that poor-metabolizing third of the patients, which would also be interesting. Lilly would presumably settle for that, although they'd like even more of the market if they can get it, naturally.
And I have to say: I like this sort of thing. I like it a lot. This, to me, is how the system should work. Companies are pursuing their own competing interests, but in the end, we get a higher standard of care by finding out which drug really works for which patients. The motivation to do all this? Money, of course, earning it and saving it. This may sound crass, but I think that's a reliable, proven method to motivate people and companies, one that works even better than depending on their best impulses. You could even build an economic system around such effects, with some attention to channeling these impulses in ways that benefit the greatest number of people. Worth a try.