A drug that aims to treat Alzheimer’s disease by targeting tau protein has failed to show a significant benefit in a phase III trial, dashing hopes of a launch next year.
TauRx’ tau aggregation inhibitor LMTX failed to meet its objective of improving cognition and the ability to carry out everyday tasks in the trial, which involved 891 patients with mild Alzheimer’s.
However, the drug was able to show an effect in brain shrinkage – reducing it by up to a third – and was able to show a cognitive benefit in a subset of patients who were not being treated with existing treatments for the disease such as cholinesterase inhibitors.
The finding in this small group of 82 patients – around 15% of the total population – is a lifeline for LMTX but raises a number of tricky questions, such as whether there is an interaction with LMTX and other drugs or there is a difference between that group and the larger study population. Given the small numbers involved it is possible of course the perceived benefits were a fluke.
TauRx has two other trials in play – one in mild Alzheimer’s disease and another in behavioural variant frontotemporal dementia (bvFTD) that are due to report later this year.
Much of the pharma industry’s efforts in Alzheimer’s have been directed at the amyloid plaques seen in the brains of patients – resulting in a string of trial failures. The reaction has been to start treating patients earlier and earlier in the course of the disease, but while there have been some signals this may have a benefit the approach is still a gamble and could result in at-risk patients being treated for decades.
Singapore-based TauRx has been one of a handful of voices calling for more effort on tau – a protein that causes characteristic tangle structures in the brains of Alzheimer’s patients that appear long before amyloid plaques are present. LMTX is thought to reduce the accumulation of the tau protein, which normally stabilizes neurons, into potentially toxic tangles.
Other companies working on tau include Eisai/Biogen who are looking at combining a tau blocker with an anti-amyloid drug, AbbVie/C2N, Bristol-Myers Squibb, AC Immune, Axon Neuroscience and Astellas. This approach has earlier failures too, however, with casualties including Zeltia’s tideglusib, BMS’ epothilome D and Allon/Paladin Labs’ davunetide.
The LMTX data were presented at the Alzheimer’s Association International Conference in Toronto. Commenting on the data, the charity’s chief scientific officer Maria Carrillo said the trial was a “hopeful sign”, particularly as it raises the possibility of combination therapy with amyloid drugs and/or those targeting inflammation in the brains of Alzheimer’s patients.