Shots: 

• Richard Stefanacci, Chief Medical Officer at TauRx, sheds light on the anti-tau drug Hydronomethylthionine mesylate (HMTM), a potential oral treatment for patients with Alzheimer’s disease and mild cognitive impairment 

• While highlighting the positive results from the LUCIDITY P-III study, Richard speaks about bridging the gap in AD and MCI treatment by lowering the dependence on intravenous therapy and advanced radiologic monitoring 

• Richard boasts of the accessibility of the treatment that HMTM offers and reveals that the company expects the complete 24-month top-line result in Spring 2024 

Saurabh: Let's start the discussion with a brief introduction of Hydromethylthionine Mesylate and its potential to work for neurodegenerative disease.  

Richard: Hydronomethylthionine mesylate (HMTM), is a potent inhibitor of tau aggregation that works by changing the conformation of the tau protein. HMTM is an oral treatment that would offer convenience for patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) due to AD. If approved, HMTM would offer a unique treatment option targeting disease progression and symptoms, rather than just easing the symptoms of the disease. HMTM has been consistently shown to have a favorable safety profile, as evidenced in thousands of patients to date.  

Saurabh: Can you please throw some light on tau proteins and their effect on Alzheimer’s Disease? 

Richard: Aggregation of tau and amyloid are both hallmark pathologies of AD and begin years before dementia symptoms emerge. Tau aggregation disrupts neuronal function. Tau tangles can be seen in the brains of patients before dementia symptoms emerge. Tau aggregation pathology correlates with the clinical decline (loss of memory and ability to care for oneself) commonly seen in people with AD, establishing it as an important target for treatment. 

Saurabh: Please let us know about the outcome demonstrated in the P-III study (LUCIDITY). 

Richard: LUCIDITY comprised a 12-month double-blind controlled Phase 3 clinical trial followed by a 12-month period in which all participants received HMTM at 16 mg/day. The trial investigated changes in various clinical and biomarker outcomes comparing HMTM 16 mg/day with methylthioninium chloride (MTC) given 4 mg twice weekly as a control over the first 12 months. Neurofilament light chain (NfL), an established biomarker for brain neurodegeneration, was the principal blood biomarker endpoint in this study.  

In July 2023 at the Alzheimer’s Association International Conference (AAIC), TauRx presented results from a prespecified analysis of the Phase 3 LUCIDITY trial that measured the impact of HMTM on NfL. Blood concentration of NfL showed a statistically significant 93% reduction in change over 12 months in participants receiving HMTM at a dose of 16 mg/day relative to the control group, which correlated significantly with a tau biomarker (p-tau 181) in blood. The NfL results demonstrate that a drug targeting tau pathology reduces the neurodegeneration that underlies clinical decline in AD. 

In October 2022 at the Clinical Trials on Alzheimer’s Disease (CTAD) congress, TauRx presented topline results from the Phase 3 LUCIDITY trial demonstrating an improvement in cognition over the pre-treatment baseline, at a dose of 16 mg/day of HMTM in participants with AD and MCI due to AD. For people with MCI due to AD, HMTM treatment resulted in sustained improvement in cognition over pre-treatment baseline, and normalisation of brain atrophy to a rate similar to healthy individuals. For people with mild to moderate AD, HMTM stabilised cognition and function and reduced rate of brain atrophy compared to historically matched individuals with AD.  

LUCIDITY is the only late-stage clinical trial specifically targeting the tau pathology of Alzheimer’s. As of Fall 2023, LUCIDITY is now complete and full 24-month topline results will be presented in Spring 2024. 

Saurabh: What are the major unmet needs that TauRx is working to address? 

Richard: AD is a global problem – it’s a disease that will affect everyone in some way at some point. Our priority is to help the millions of people living with AD/MCI and their families with the development of a safe and effective treatment that they will be able to access. As an oral safe treatment, we are absent the burden of intravenous therapy and advanced radiologic monitoring.  

Saurabh: How is Hydromethylthionine Mesylate better than already available treatment options (incl. Recently approved Alzheimer’s treatment option) and does TauRx plan to do any future Head-to-Head study to prove the superiority?  

Richard: Because HMTM is taken in tablet form and has a strong safety profile, it could provide a readily accessible treatment option for people with mild to moderate AD and MCI due to AD. No patients in our study have suffered treatment-related serious adverse events.  

To our knowledge, at this time, no head-to-head study are planned but we welcome those studies being carried out in the future. For now, our priority is to help the millions of patients with AD/MCI due to AD and their families with the development of a safe and effective treatment that they will be able to access.  

Image Source: Canva 

About the Author: 

Dr. Richard G. Stefanacci 

Dr Stefanacci is a practicing internist/geriatrician with a focus on care of persons with Alzheimer’s. He served as Health Policy Scholar for the Centers for Medicare & Medicaid Services (CMS) where his work focused on medication access and served on the Medicare Part D reg writing team. He has combined his expertise in healthcare policy in his teaching position at Thomas Jefferson University in their Jefferson College of Population Health. In his academic role he has well over 600 publications in addition to delivering well over 1000 lectures both nationally and internationally. Dr Stefanacci has achieved recognition as a fellow in both the College of Physicians of Philadelphia and American Geriatric Society as well as several national awards. 

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