“Despite this latest setback, Eli Lilly remains committed to plunging through this concrete wall headfirst. This is a sad day for our WallBreaker 2020 program, and some of our longtime head bashers will recall similar periods during SkullButt 2012 and ConcreteCracker 2016. But we continue to believe that the only way past this wall is straight through it, with all the force that our craniums can bring to bear.
Our partners in this latest attempt, AstraZeneca, realized in 2014 the importance of plunging with great force into the same structure. But they said “Hey, our heads aren’t just going to bash themselves into this massive edifice – we need to take a big running start and come in with perfect 90 degree orthogonal form.” And they knew to come to the leaders in the field: Eli Lilly. After all, our gamma-secretase inhibitor completely failed in 2010. Then we took our antibody, solanezumab into Phase III trials that failed in 2012. And found out in 2013 that our beta-secretase inhibitor failed. But then we kept plunging on and reported almost identical results for solanezumab in 2015 and 2016. No one knows more about direct, head-on contact with the amyloid hypothesis than Eli Lilly.
So now the Lilly/AstraZeneca beta-secretase inhibitor has failed in turn. But we remain steadfast. If there is any way left to send our ourselves full-tilt into another failed amyloid trial, our pledge to you is that Lilly will find it. There is somehow enough money to fuel the cash-burners that power the steam-driven catapults. We have plenty of helmets, whose dents are even now being pounded out. And most of all, we have our beloved wall, which we shall never forsake. Higher velocity! More power! Once more into the concrete, my friends! Who’s with me?”
Editorial note: as mentioned before, I actually have a lot of respect for Lilly putting as much time, effort, and money into their Alzheimer’s work as they have. But geez. At some point, the dedication to one particular hypothesis, in the face of mounting evidence of trouble, becomes a bit less deserving of admiration
Neither do I intend to make light of the situation faced by Alzheimer’s patients and caregivers (I’ve seen what it can do). But anyone who was holding out for this trial to come through with a cure was sadly misinformed. The amyloid hypothesis is in deep trouble. folks. It’s been in trouble for years. Multiple attempts (and not just by Eli Lilly!) to turn it into something of clinical utility have failed. Biogen, I’m talking to you, too. You have (of all things) an amyloid antibody deep into clinical trials that you have bet a substantial part of your future on. How did you let this happen? Are you happy about it? Are you optimistic?
And all this goes for any other group that’s betting on amyloid inhibition of some sort to make a clinical difference in Alzheimer’s. Yes, yes, unmet medical need, yes, huge market, yes, all that. But look around you. Are you optimistic? And if so: why?