TAIs Show Promise in Disease Modification

TauRx has evaluated its first-generation tau aggregation inhibitor (TAI), rember®, in a large, double-blind, long-duration, Phase 2 clinical trial in 321 patients with mild or moderate Alzheimer’s disease. This study provided the first clinical indication that treatment with TAIs holds promise in modifying the progression of the disease.

In this study, rember® showed a significant reduction in the rate of clinical decline: 80% by weeks 50 and 102 relative to controls, as measured using psychometric tools. The graphs below show the stable treatment effect in both the combined mild/moderate population and in the mild subject subgroup who elected to continue in the study up to two years (blue lines).

Clinical Trials Phase 2

Functional neuroimaging results from the trial supported the psychometric data: in patients taking rember®, the loss of function in the areas of the brain known to be particularly affected by the tau tangle pathology of disease was eliminated over 6 months. Functional brain scan benefits seen at 6 months were predictive of clinical benefit at 12 months.

Phase 2 Results Lead to Second-Generation TAI Development

The Phase 2 study, and subsequent Phase 1 studies, also showed that there are limitations in the absorption of the active component of rember®, methylthioninium (MT), when it was given in the charged MT+ form. In the Phase 2 study, this problem was exacerbated by a capsule formulation defect which particularly affected the highest dose tested. MT+ must be converted to the uncharged leuco-MT form (LMT) by a thiazine reductase enzyme in the low pH of the stomach before it can be absorbed at higher, more therapeutic doses. However, in order to be tolerable at higher doses it needs to be given with food, which impairs the reductase activity needed for conversion to the LMT form and thereby limits absorption.

This finding led to the development of TauRx’s second-generation TAI LMTX®, which is a stable, reduced form that delivers MT without the need for active conversion in the stomach. In Phase 1 studies, LMTX® was found to be well tolerated at much higher doses than those used in the Phase 2 study.


Wischik CM, Staff RT, Wischik DJ, et al. (2015) Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer's disease. J Alzheimers Dis 44(2):705-20.

Phase 2 Imaging - Read more