Two-Year LUCIDITY Trial Data Show Sustained Cognitive Benefits, No Increased Risk of ARIA
New 24-month data from the Phase 3 LUCIDITY trial of hydromethylthionine mesylate (HMTM) show sustained benefits across the disease spectrum from early to moderate dementia. Analyses comparing the study participants to closely matched real world data and meta-analytical controls, showed significantly reduced disease progression in participants in the LUCIDITY trial. In the early disease subgroup there was a significant reduction in transition to the dementia stage of AD. HMTM has a benign safety profile in approximately 3000 subjects studied in trials and has shown no increased risk of amyloid related imaging abnormalities. TauRx Pharmaceuticals Ltd. presented the data at the AD/PD 2024 Alzheimer's & Parkinson's Diseases Conference in Lisbon, Portugal.
HMTM is a tau aggregation inhibitor designed to reduce tau pathology in AD. LUCIDITY compared change in standard cognitive and functional outcomes and brain volume loss in participants with early stage to moderate AD treated with HMTM at a 16 mg/day dose with a control group over 12 months, followed by an open label phase where everyone received 16 mg/day HMTM for a further 12 months. Blood based biomarker data announced last year showed that HMTM 16 mg/day produced a 95% reduction in change in blood concentration of neurofilament light chain (NfL) relative to the control group (p=0.0291). NfL in blood provides a measure of progression of neurodegeneration in the brain.
From the new data shared , participants at the early stage of AD receiving HMTM 16 mg/day remained significantly above baseline to 18 months and only returned to baseline values after 24 months. Within this subgroup, progression of symptoms to the dementia stage of the disease was significantly less than in the control group. Additionally, further analysis of this subgroup shows that the control group declined significantly below their baseline despite the switch to 16 mg/day after 12 months in the open label phase (p=0.0308 for the observed cases difference in ADAS-Cog13, being a more accurate measure for early disease).
Commenting on the results, Professor Claude Wischik, CEO and Executive Chairman of TauRx, explains, “The new data show that benefit can be maintained over 24-months and highlight the importance of starting HMTM treatment early in the disease process. The results are also consistent with earlier research showing that HMTM combines two independent modes of action: inhibition of tau aggregation pathology in the brain and a second symptomatic activity. We were surprised to find that the blood concentration of active drug follows an atypical profile over 12 months reaching levels sufficient for symptomatic activity even at a very low dose.
“There is strong evidence HMTM impacts the underlying tau pathology of AD. When we compared our results with natural history real world data, such as from the Alzheimer disease Neuroimaging Initiative1 database and meta-analytic controls from placebo arms of multiple AD trials in similar patient populations, we found statistically significant differences in cognitive and functional outcomes supporting the benefits of HMTM. With the combination of a strong safety profile and accessibility offered by an orally administered drug, HMTM presents as a unique potential treatment option for patients and physicians.”
Professor Alistair Burns, Emeritus Professor of Old Age Psychiatry at the University of Manchester and previously England’s National Clinical Director for Dementia, observed, "We have reached an exciting time in the field of Alzheimer disease treatment. After no new therapies for a generation, we are on the threshold of having a range of new treatments, including a tau-targeted oral therapy, which have the real potential to slow the disease process. This is great news for people with Alzheimer disease, their families and careers."
In light of data shared, HMTM has prospective broad applicability for a wide demographic contributing to equity of access to new treatment options. TauRx has initiated regulatory engagement in the UK and the US for intended product approval.