Failure after failure has been the story on amyloid-targeting therapies in Alzheimer’s. Tau protein, which is involved in pathology of its own in the disease, has been less in the spotlight (although TauRx has done its part by missing its clinical endpoints with its own drug).
But there’s a lot of activity going on with tau these days. Merck just announced that they’re buying the rights to Teijin Pharma’s tau antibody therapy, which has gotten some attention. AC Immune has a deal with J&J on a tau antibody program of their own, and AbbVie is going into Phase II with an anti-tau antibody as well (also inlicensed). Bristol-Myers Squibb had another anti-tau program going, but that one has just been licensed to Biogen. On the small-molecule end of things, that first link in the paragraph details a number of attempts at kinase inhibitors (to slow down tau hyperphosphorylation) and small-molecule aggregation inhibitors (which is where TauRx came to grief).
It’s unfortunately going to be quite a while before we see what any of the agents do – such is the course of Alzheimer’s in the clinic. I have no idea what the prospects are, but it would appear that several companies have decided that another crack at amyloid is not the way to go. Considering the relentless string of brutally expensive failures in that area, they probably have a point. In this case, better the devil you don’t know than the one that you’ve come to know too well.
Update: as suggested here, what the tau trials will have to avoid is wishful thinking. That paper suggests that some of the previous amyloid antibody trials never should have gone as far as they did:
An analysis of publicly available data from the Phase II studies for bapineuzumab and solanezumab indicates that neither compound produced compelling evidence of drug-like behavior that would justify their progression into pivotal trials. The published data suggest that sponsors took decisions to move these compounds into Phase III on the basis of vastly limited data that were rife with type I error and probably driven by commercial concerns.
Probably, indeed. There are moral hazards in this area, all of which can be sold to oneself as trying to do everything one can to help patients.