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Anyone looking after someone with dementia, particularly Progressive Supranuclear Palsy (PSP), can not fail to be disappointed by the recent failure of Davunetide in a phase III trial. Allon therapeutics announced just before Christmas that no clinical endpoint had shown improvement.

Whilst this is one in a growing line of failures for disease modifying treatment in dementia, some would argue Davunetide had more chance than its predecessors. Firstly, it targeted the tau protein, which builds up in and woman-taking-pills-medicine-628x363around the neurons of people with PSP. No doubt Allon were hoping that it would work, and then be taken in to trials of Alzheimer’s disease where tau is also found. Most previous drugs trials in Alzheimer’s disease have focused on beta-amyloid, another protein that can build up in the brain, but which is less certain to be a central part of the disease process and may be a tombstone of other events (for example see here). In PSP there is no amyloid, so targeting tau, and only tau, was supposed to work.

Most disappointing is that none of the secondary or exploratory endpoints showed any signs of change, although we are not told what these were. When designing a drug study, it is usual to pick hard clinical measures as a primary endpoint. I would have been hugely surprised if the primary endpoints had changed, given that the disease process in PSP is rather fast, and slowing it down once symptoms have developed is like stopping an out-of-control roller coaster. But perhaps Davunetide could have at least made a few dents in other measures, hinting that the approach to target tau was correct. I’m afraid we’re not given that comfort.

Does that mean it’s all been worthless? No. Each clinical trial has useful data in it, even if that data is not what we would wish to see. I do hope the full results see the light of day. Those who know me well also know I do not have a soft spot for drug companies. But I feel genuinely sorry for Allon. They are a relatively small company and this (commercial) failure has come as a big blow both in share price and job losses. I’m not sure whether the company can survive. If Allon does go under, I wonder what will happen to the data. The press release commented on further investigation as to why the drug didn’t work, my hope is this will be in the open and not behind closed doors under the defence of ‘commercial interests’. I’d love to get my hands on it if I could!

It is natural to pick on tau and beta-amyloid as targets for slowing down the disease. Both proteins are easily seen under even the simplest microscope, and have a long track record in lab and animal experiments. But we need to be more savvy about how we develop drugs in the future, targeting multiple pathways and developing drugs that target disease mechanisms we can’t see. This means new disease measures and new drug discovery techniques (that’s a whole different blog!). I only hope we have some encouraging news before the pharma industry turns its back on dementia completely.