Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine . All content is Derek’s own, and he does not in any way speak for his employer.

For the past several years, a clinical trial from Washington University (St. Louis) has been underway in people with genetic mutations that lead to early-onset Alzheimer’s. The Dominantly Inherited Alzheimer’s Network (Trials Unit), DIAN-TU, has been dosing 194 such patients with one of two anti-amyloid antibodies, either Lilly’s solanezumab or Roche/Genentech’s gantenerumab (or placebo), and looking for signs of slowing cognitive decline. Here’s a blog post back when that started.

Results were announced today, and sadly you already know what they are. No effect for either drug, the doses of which were increased over time. I’ve written several times about solanezumab here over the years (most recently here), and it has an unbroken record of clinical failure. Lengthy, expensive, complete clinical failure, and this latest trial is more of the same. Gantenerumab is the same: never a sign of benefit. The unusual thing about this trial was that it was a preventative effort in people whose genetic background makes their development of Alzheimer’s virtually certain, and was thus started in patients very early. Another such effort has been going for some years now in a patient population in Colombia, with another Roche/Genentech antibody (crenezumab). Baseline data have been released from that one, but (to my knowledge) no treatment results. Odds of a beneficial effect of treatment must at this point be rated as extremely small.

I really don’t know what else to say at this point. I’ve been writing this blog since 2002, several years after my own experiences with Alzheimer’s drug discovery, and ever since then I have chronicled the failure of drug after drug aimed at the amyloid hypothesis. Different mechanisms, different dosing, different patient populations, different trial designs: none of it has worked. Not once. I myself include the most recent Biogen/Eisai antibody efforts in that list – yes, the one that they’ve submitted to the FDA and are trying to get approved, a decision about which I have made my position abundantly clear.

Today’s announcement doesn’t bear directly on the Biogen/Eisai results – different antibody, different patient population – but it does dump another shovelful of cold dirt on the entire idea of treating Alzheimer’s disease with such amyloid-targeting antibodies. Nothing has ever worked. Never once. So when another effort comes along with another antibody, whose initial results were a clear failure (as stated by the investigators themselves), is this a surprise? Not at all: the surprise was when Biogen came back around and said that gosh, a re-examination of the results makes them think that they stopped the trial too early, that if you stand at a particular angle at a particular time of day it almost looks like something was starting to work. Squint, they say. It’s there.

As that last-linked blog post makes clear, I don’t find that evidence compelling, and most certainly not compelling enough to approve the drug as it stands. But with the way the FDA is behaving these days, God only knows what’s going to happen. People are investing on just that basis, although rarely stated in quite those words. But if you can look at the ruins of all the attempts to show efficacy with anti-amyloid antibody therapies and decide that the Biogen/Eisai data represent a real ray of hope, you have a sunnier disposition than I do.