After years of work and untold amounts of money, Eli Lilly’s Alzheimer’s antibody, solanezumab, does not work. It does not help Alzheimer’s patients. No matter how many times you run the Phase III trials, or in which patient populations, they do not get better. No matter how many hopeful press articles you might have seen on its prospects and no matter how many statements you might have seen from the company itself, no matter how you may try to spin the results, it does not do anything useful when you give it to actual Alzheimer’s patients. The program is over. It is done, because it does not work.
I’m so adamant because Lilly has been banging away on this drug for years now, hugely and expensively, which in one way does them some credit. Alzheimer’s is an insanely risky field to work in, what with the (basically zero) success rate, and the company deserves a lot of credit for taking it on. But what they do not deserve a lot of credit for is the way that they’ve been giving people to understand that yes, there’s hope, and yes, it’s actually working, and yes, the next trial could really be it.
And the press, at least a lot of the press, went along with this (especially in Britain). But over here in the US, we had “glimmer of hope“, “raised hopes“, “exciting possibilities“, and “will soon offer hope“. The most irresponsible headlines, though, were in the UK press, for reasons I’ve never quite understood. Meanwhile, during all this glimmering and hoping and excitement, most people who actually follow the field were in “You know, that doesn’t seem to have done much of anything” mode. I’m not criticizing Lilly for going ahead and seeing if solanezumab actually worked, although you could argue that this was an expensive long shot. But not enough people got the word about how long a shot it really was.
This news is also bad for Biogen, because they have a competing amyloid antibody in the works, and honestly, so far it’s not making anyone very hopeful, either. Antibodies are all different, so you can’t be sure, but this can’t be a good sign, and I (for one) will be very, very surprised if they get any convincingly good data when it’s all over. We’ll see.
Finally, this news is yet another whack at the entire beta-amyloid hypothesis for Alzheimer’s therapy. One of the key things that we might get from this latest Lilly trial is whether they saw signs of amyloid clearance/decreased amyloid aggregate formation in their patients. If they did, and if these patients didn’t get any better – and they didn’t – then where does that leave us? Trial after trial, mechanism after mechanism, and things always come up short. At some point, we’re all going to have to stop making excuses (not potent enough, bad PK, not selective enough, not the right patient population, didn’t run long enough!) Everyone’s always known that the entire beta-amyloid hypothesis could be wrong – a hypothesis always can be wrong. But facing up to what that means has been another thing entirely. You may not think that we’re at that point yet, and I can’t quite say that we are, but at some point we’re going to be at that point. Right?