Another Prospective Alzheimer's Trial

Includes: LLY, RHHBF
by: Derek Lowe

I wrote here about a prospective Alzheimer's trial that's starting soon among a population in Colombia, and now comes word of another large effort along the same lines.

DIAN, the Dominantly Inherited Alzheimer's Network, will test several current Alzheimer's candidates in groups of people around the world with genetic mutations that make them susceptible to the disease. The hope is that these different mutations will provide a fast-forward-button look at the progress of Alzheimer's in the general population, and help to settle the question of which mechanisms (if any) are appropriate to fight it. They'll go two years of clinical observation (memory tests and brain imaging), and then the plan is to switch everyone to the most efficacious therapy and continue monitoring for real-world benefits.

Currently it looks as if there will be three candidates, with two from Eli Lilly (NYSE:LLY): the beta-secretase inhibitor LY2886721 and the circulating-amyloid antibody Solanezumab, currently the subject of controversy regarding its efficacy or lack of same. The Roche (OTCQX:RHHBF) antibody gantenerumab, which appears to bind more to amyloid that's already precipitated, completes the trio.

This is an excellent idea, and I'm very glad to see so much work being done on prospective trials like these. There's always the danger that working in genetic-mutation populations will give you an answer that's not generally applicable, but I think that we know enough about the specific mutations to make a call on that should anything stand out. The worry, naturally, is that nothing will stand out. The DIAN trial and the Roche crenezumab trial in Colombia are all aimed at various parts of the amyloid hypothesis, which has been the dominant strain of thought in Alzheimer's etiology for decades. If nothing distinctive comes out of these efforts, that hypothesis will have taken some major hits -- but they'll have to be major hits to damage it in the first place.

The best result will be if something looks useful in preventative or early-stage Alzheimer's. Second best would be a painful realization that the amyloid hypothesis is insufficient. And way down at the bottom would be a bunch of "Well, maybe..." clinical data showing that some of the agents seemed to help some of the patients some of the time, to an extent, but maybe not enough to be effective by real-world standards. Anything but that, please.

Disclosure: None.