Over the years of this blog, I’ve occasionally made comments about how no one really knows much about how drugs for the major central nervous system diseases work. Well, actually, I’ve stated things more forcefully than that, but you get the idea. And although many people who work in the area have written in to say that they agree, I’ve had questions from people completely outside it (journalists and others) about whether I’m serious when I say these things.
Oh, I am. For the latest piece of evidence, see what’s just happened to LY2140023, Eli Lilly’s (NYSE:LLY) new drug candidate for schizophrenia. The company was running a three-armed Phase II trial: placebo vs. their existing drug Zyprexa vs. the new one, which is a metabotropic glutamate ligand. And what happens? The placebo group performs about twice as well as the usual average in such trials, for some reason. And that not only swamped the investigational drug, but Zyprexa as well, which has been on the market for years.
Now, there's been a lot of argument about whether the current generation of antipsychotic drugs is really better than the older ones. But I believe that they're all supposed to come in better than a placebo. As Lilly points out, though, "inconclusive trials are common in neuroscience", and they're going to run another one and hope that the patients don't all start improving again on powdered sucrose or whatever the placebo was. But this is especially surprising (and disappointing) because an earlier Phase II trial, run in a very similar design to the latest one, showed the compound working very well indeed. How do you go from such impressive results to no better than placebo in the same sort of trial design? Easy - just make sure that you're developing a drug for schizophrenia. Or depression. Or chronic pain, or Alzheimer's. Stick with the central nervous system, and your drug discovery career will never be boring.
Oh, and one last note: after all the recent stories about buried clinical results, I'm glad to see a company fall completely flat with one of its most promising drugs - and then get up at a large scientific meeting and tell everyone about it in detail. It's not that it's so unusual, but it's good to show people that it happens, and how it's handled when it does.