LUCIDITY Trial Shows 2-Year Cognitive Benefits of HMTM in Alzheimer's Disease

Hydromethylthionine mesylate (HMTM), a drug developed by TauRx Pharmaceuticals, is designed to intervene early in the disease process of Alzheimer's, aiming to slow its progression. The compound has demonstrated a favorable safety profile across nearly 3,000 subjects in trials, showing no heightened risk of amyloid-related imaging anomalies. It is being positioned as a potential first oral therapy against tau protein, requiring minimal testing and monitoring for Alzheimer's disease treatment.

TauRx Pharmaceuticals, a frontrunner in research related to tau proteins in Alzheimer's, recently unveiled 24-month data from the Phase 3 LUCIDITY trial of HMTM at a conference in Lisbon. The study showed sustained benefits across the spectrum of the disease, from early to moderate dementia stages. Participants in the LUCIDITY trial experienced a significant reduction in disease progression compared to real-world data and meta-analytical controls. Notably, the early disease subgroup saw a marked decrease in the transition to dementia.

HMTM functions as an inhibitor of tau aggregation, a key pathological feature in Alzheimer's disease. The LUCIDITY trial compared cognitive and functional outcomes, along with brain volume loss, in patients with early to moderate Alzheimer's treated with HMTM at a dosage of 16 mg/day against a control group over a period of 12 months. This was followed by an open-label phase where all participants received the same dosage for an additional 12 months. Prior biomarker data indicated that HMTM at 16 mg/day resulted in a 95% reduction in the change of blood neurofilament light chain (NfL) concentration relative to the control group, a biomarker for neurodegeneration.

The latest findings reveal that patients in the early stages of Alzheimer's who received HMTM maintained significantly above baseline levels up to 18 months, reverting to baseline only after 24 months. The progression to dementia was significantly less in this group compared to the control group. Further analysis showed a significant decline in the control group despite switching to HMTM after 12 months.

Professor Claude Wischik, CEO of TauRx, highlighted the importance of initiating HMTM treatment early and emphasized the drug's dual action: inhibiting tau aggregation in the brain and offering symptomatic relief. The drug's blood concentration profile over 12 months was atypical, reaching levels sufficient for symptomatic activity even at low doses.

The evidence suggests that HMTM impacts the underlying tau pathology of Alzheimer's. When compared with natural history data and meta-analytic controls from placebo arms of similar trials, there were statistically significant differences in cognitive and functional outcomes, supporting HMTM's benefits. With a robust safety profile and the convenience of oral administration, HMTM presents a unique treatment option.

Professor Alistair Burns, an expert in the field, noted the significance of the development of new treatments, including tau-targeted oral therapies, which could slow the disease process, offering hope for patients and their caregivers.

TauRx has begun regulatory discussions in the UK and the US for product approval, with plans to expand to other territories as part of the commercialization strategy for HMTM. The company, founded in 2002 with operations in Aberdeen, UK, has been dedicated to developing treatments for Alzheimer's and other neurodegenerative diseases caused by protein aggregation. With the LUCIDITY trial's findings, TauRx is poised to contribute to the global effort to address Alzheimer's disease, with future research planned for related conditions.