Eli Lilly has been testing their solanezumab antibody against Alzheimer’s for some years now. The first rounds of clinical trials were. . .inconclusive at best. Perhaps there was a bit of an effect in the mildest-affected patient cohort, perhaps not. The company went for it, though, starting a second Phase III in a more carefully selected population. As I and many other people have noted, the company is very nearly being bet on Alzheimer’s, in a series of very expensive clinical programs on this and other agents, so the progress of this trial is a big issue for Lilly and its shareholders.
That would explain why they’re down about 5% this morning. The company has issued a press release saying that they’re changing the primary endpoint of the trial:
The original study design included co-primary endpoints of cognition and function—measured by ADAS-Cog14 (Alzheimer’s Disease Assessment Scale-Cognitive subscale) and ADCS-iADL (Alzheimer’s Disease Cooperative Study-Instrumental Activities of Daily Living), respectively. Emerging scientific evidence supports the idea that cognitive decline precedes and predicts functional decline in Alzheimer’s disease, particularly in earlier stages of the disease. Thus, Lilly has decided to amend the EXPEDITION3 trial to include a single primary endpoint of cognition (ADAS-Cog14). Functional outcomes will be measured during the trial in the same manner as previously designed, using both the ADCS-iADL and the FAQ (Functional Assessment Questionnaire). These two functional outcomes will now be considered key secondary endpoints for the EXPEDITION3 study.
I’m not enough of a neurologist to say how much of a big switch this is, but I do know, from the drug discovery end, that you don’t change the primary endpoint of a huge clinical trial without a very good reason. Problem is, there are two compelling reasons that come to mind (and they’re not mutually exclusive, either). One is that, as the press release states, that the trial really does need to be looking at cognition, and that it would be irresponsible not to recognize that and act accordingly. The other, though, is that the company fears that the trial as launched is in danger of missing its original primary endpoint, and has decided that since a case can be made for a cognition endpoint and that it has a better chance of yielding something positive.
It all comes down to the idea that cognition is truly a sound marker for functional effects. Is it? Investors clearly have some fears that it isn’t, but I’m going to be interested to hear the reaction from the rest of the Alzheimer’s research community. Is Lilly doing the right thing, or are they gasping for air?