Hydromethylthionine mesylate

The application for HMTM to treat Alzheimer’s is based on data from Phase III LUCIDITY trial and two prior Phase III studies. Credit: CGN089 / Shutterstock. TauRx Pharmaceuticals has filed a marketing authorisation application (MAA) with the UK Medicines and Healthcare products Regulatory Agency, seeking approval for hydromethylthionine mesylate (HMTM) to treat Alzheimer’s disease (AD). HMTM is intended for treating mild cognitive impairment due to Alzheimer’s disease (MCI-AD) and mild to moderate dementia stages associated with AD. The UK regulator had previously designated the innovative licensing and access pathway for HMTM. The UK could become the first country to offer this oral treatment on approving HMTM. TauRx’s MAA for the asset is underpinned by comprehensive evidence from the 24-month Phase III LUCIDITY clinical trial and two previous Phase III studies. See Also: Pharma M&A: The top high value deals in 2023 Medical packaging companies in pharmaceutical contract manufacturing These trials consistently demonstrated HMTM’s benefits in slowing cognitive decline, maintaining daily living activities and reducing brain atrophy rates. Tau aggregation, a key factor in Alzheimer’s, correlates with cognitive decline severity and brain nerve cell damage. HMTM counters this by selectively inhibiting tau-protein aggregation. Designed as an oral AD treatment, HMTM targets tau aggregation and enhances brain function through a secondary, tau-independent action that raises acetylcholine levels in the hippocampus. The global Phase III LUCIDITY trial involving over 3,000 subjects has concluded and established the safety profile of HMTM. A notable finding from the LUCIDITY trial was the significant reduction in neurofilament light chain, a biomarker for neurodegeneration, at the 12-month mark of the study. Clinical assessments of cognition revealed sustained improvements from baseline over 18 months in MCI-diagnosed patients. TauRx executive chairman professor Claude Wischik stated: “This is a significant milestone for TauRx and is an important step in potentially bringing a new type of treatment and a new hope to patients and families who carry the burden of this terrible disease.”

HMTM is designed for early intervention to modify the underlying disease process and slow progression of Alzheimer’s disease HMTM has a benign safety pro approximately 3000 subjects studied in trials and has shown no increased risk of amyloid related imaging abnormalities HMTM holds potential to be the first oral, anti-tau therapy requiring minimal testing and treatment monitoring for the treatment of Alzheimer’s disease ABERDEEN, Scotland--(BUSINESS WIRE)-- TauRx Pharmaceuticals Ltd., a global leader in tau-based research in Alzheimer’s disease (AD), presented the 24-month data from its Phase 3 LUCIDITY trial of hydromethylthionine mesylate (HMTM) at the AD/PD™ 2024 Alzheimer's & Parkinson's Diseases Conference in Lisbon, Portugal. This press release features multimedia. View the full release here: Co-founder and CEO, Professor Claude Wischik (Photo: Business Wire) New 24-month data 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 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 data shared today, 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 pro 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’s 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 HMTM2. With the combination of a strong safety pro 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’s 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's disease, their families and carers." 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. Other territories will follow in line with plans to scale commercialisation of HMTM. For additional information, please visit: or . References: 1. ADNI, ; 2. P-values for difference in ADAS-Cog11 at 24 months was p=0.035 and for whole brain volume MRI at 24 months 0.004 when results of HMTM treatment group arm is compared to matched ADNI. P-values for all results comparing HMTM treatment with placebo arms of other studies over 18 months were p<0.0001. TAU PATHOLOGY IN ALZHEIMER’S Through dedicated research programs, it is understood that certain age-related factors lead to misfolding and aggregation of tau proteins, and the subsequent formation of tau tangles in Alzheimer’s. Pathological aggregation of tau protein disrupts and damages neuronal function. The process begins many years before symptoms of dementia are seen. Tau pathology has been proven to correlate with the clinical decline (loss of memory and ability to care for oneself) commonly seen in people with Alzheimer’s, establishing it as an important target for treatment. HMTM is primarily a tau aggregation inhibitor, which effectively crosses the blood brain barrier to target the source of this damaging process. Its secondary pharmacological action is symptomatic through increasing acetylcholine levels in parts of the brain essential for memory functions. ABOUT LUCIDITY Completed in June 2023, LUCIDITY was a double-blind randomised controlled Phase III clinical trial comparing change over 12 months in cognitive, functional and brain atrophy outcomes at HMTM doses of 16 mg/day, 8 mg/day and methylthioninium chloride (MTC) at a dose of 4 mg twice weekly as a control in a 4:1:4 randomisation, with a subsequent 12 month blinded open-label extension phase in which all participants received 16 mg/day. MTC 8mg/week was used in the control group to maintain study blinding for slight urinary colouration, which is a known harmless side effect of the drug. Measurements of ADAS-Cog11, ADCS-ADL23, and whole brain volume MRI were taken at 12 and 24 months compared to baseline. ABOUT TAURx PHARMACEUTICALS LTD TauRx was founded in 2002 in Singapore, with primary research facilities and operations based in Aberdeen, UK. The company has dedicated the past two decades to developing treatments and diagnostics for Alzheimer’s and other neurodegenerative diseases due to pathological aggregation of tau and other proteins. Alzheimer’s disease is a leading cause of disability and death throughout the world and is one of the most important global public health issues. TauRx will contribute to addressing this unmet need with data from LUCIDITY and pursuit of regulatory approvals in line with its overall plans to make HMTM available for people living Alzheimer’s. Future research is planned for other related neurodegenerative diseases.