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October 17, 2008
Down The Chute in Phase III
Here's a good article over at the In Vivo Blog on this year's crop of expensive Phase III failures. They've mostly been biotech drugs (vaccines and the like), but it's a problem everywhere. As In Vivo's Chris Morrison puts it:
Look, drugs fail. That happens because drug development is very difficult. Even Phase III drugs fail, probably more than they used to, thanks to stiffer endpoints and attempts to tackle trickier diseases. Lilly Research Laboratory president Steve Paul lamented at our recent PSA meeting that Phase III is "still pretty lousy," in terms of attrition rates -- around 50%. And not always for the reasons you'd expect. "You shouldn't be losing Phase III molecules for lack of efficacy," he said, but it's happening throughout the industry.
Ah, but efficacy has come up in the world as a reason for failure. Failures due to pharmacokinetics have been going down over the years as we do a better job in the preclinical phase (and as we come up with more formulation options). Tox failures are probably running at their usual horrifying levels; I don't think that those have changed, because we don't understand toxicology much better (or worse) than we ever did.
But as we push into new mechanisms, we're pushing into territory that we don't understand very well. And many of these things don't work the way that we think that they do. And since we don't have good animal models - see yesterday's post - we're only going to find out about these things later on in the clinic. Phase II is where you'd expect a lot of these things to happen, but it's possible to cherry-pick things in that stage to get good enough numbers to continue. So on you go to Phase III, where you spend the serious money to find out that you've been wrong the whole time.
So we get efficacy failures (and we've been getting them for some time - see this piece from 2004). And we're getting them in Phase III because we're now smart and resourceful enough to worm our way through Phase II too often. The cure? To understand more biology. That's not a short-term fix - but it's the only one that's sure to work. . .
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