Exploring a New Oral Option for Alzheimer Treatment With Sonya Miller

Sonya Miller

In late-2022, TauRx announced positive 12-month findings from its phase 3 LUCIDITY study (NCT03446001) testing hydromethylthionine mesylate (HMTM), an investigational tau aggregation inhibitor, in a diverse patient population ranging from mild cognitively impaired to moderate Alzheimer disease (AD). The study, which tested 16-mg doses of HMTM against methylthioninium chloride as an active placebo, showed positive effects on cognition and functional decline, with minimal declines of 1.3 units and 1.0 units, respectively, on Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) and Alzheimer’s Disease Cooperative Study-Activities of Daily Living.

Years later, at the 2025 AD/PD International Conference on Alzheimer’s and Parkinson’s Diseases, held April 1-5 in Vienna, Austria, a symposium session covered challenges in targeting tau, with TauRx presenting new data further confirming the efficacy of HMTM in early to moderate AD. Given by TauRx chief executive officer Claude Wischik, the data further demonstrated how HMTM at doses of 16 mg/day is effective in reducing clinical decline and brain atrophy progression in this patient population over a 78-week period, with clinically meaningful treatment benefits lasting 2 years.

Following the meeting, NeurologyLive^® caught up with Sonya Miller, medical director at TauRx, to discuss promising results from LUCIDITY presented at AD/PD 2025. In the conversation, she outlined the design and approach to this analysis, the notable cognitive and functional benefits observed, and some of the safety profile of HMTM to date. In addition, Miller provided insights on the drug’s formulation and how its broad patient applicability may help distinguish it from many currently available treatments. Furthermore, she gave commentary on the future plans for the drug, and its place within the evolving AD treatment landscape.

NeurologyLive: Can you outline the most notable findings from the study, including the biggest takeaways clinicians should have?

Sonya Miller: HMTM is potentially the first oral treatment for Alzheimer's disease which targets tau protein pathology. The consistent results across analyses comparing HMTM from the pivotal LUCIDITY study with external data show the treatment is effective in reducing clinical decline and brain atrophy progression. This is over a period of at least 18 months with the potential to continue meaningful benefits lasting up to two years.

We have conducted four global Phase 3 randomised clinical trials in AD and Frontotemporal dementia (FTD), and while many other AD trials have focused solely on MCI, our inclusion criteria encompassed both MCI due to probable AD as well as mild to moderate AD.

Our latest analyses compared results from HMTM’s recent LUCIDITY Phase 3 trial with placebo data from closely matched subjects available from the Critical Path in AD (CPAD) Institute database, which contains information from nearly 10,000 patients that have taken part in 36 global trials.

This showed benefit in cognition as measured by both ADAS-Cog and CDR-SB, in function as measured by ADL and in the objective biomarkers, notable WBV. Beneficial results were seen as early as six months, with sustained benefit at 18-24 months. This is supported by strong blood biomarker evidence; NfL and pTau217.

What is the mechanism of HMTM? How does it differ from what’s on market and why do we believe it can be a successful agent in treating Alzheimer’s disease?

HMTM belongs to a class of drugs known as Tau Aggregation Inhibitors (TAIs). TAIs prevent and dissolve tau aggregates in the brain, preserving the normal tau function essential for a healthy brain. By undoing the tangles that cause dementia, we aim to slow and potentially stop memory loss and other symptoms associated with Alzheimer’s disease.

The market differentiation comes with the application of the therapy, which is oral rather than intravenously administered, therefore being more convenient and less invasive for patients and their caregivers. We also believe it has huge cost saving benefits due to this methodology.

Dementia doesn’t discriminate, so having a treatment that is open to as many people as possible is a critical element of our work.

What is the significance of reducing brain atrophy over a long-term period? What does this tell about the therapy?

By slowing and halting the progression of brain atrophy – the loss of brain cells (neurons) and the connections between them – we can have a positive impact on the cognitive function in a patient.

Our research has shown that HMTM has the potential to “interrupt” the disease pathway and thus the death of otherwise healthy brain cells. The loss of brain cells equals loss of cognition and function, something that is irreversible – once a brain cell dies it is never retrievable. Preservation of brain cells and therefore a person’s ability to continue to function well, is crucial in treating this disease.

How did the safety profile look for this agent? Any considerations clinicians who treat patients should know about?

The safety profile, which has been gathered from over 3,000 trial participants and those on our expanded access program, has been demonstrated to be strong with some patients taking HMTM for over 10 years. As well as the drug’s oral form, we believe the robust safety profile will mean minimal patient, family and physician burden. There is no need for expensive nor invasive safety monitoring and patients can safely take this medication at home exactly as they would do for other standard treatments.

Usual medical co-morbidities and medications are not exclusionary for using HMTM. The only exclusion is known allergy to any excipients, which is standard for all medications, and any history of haemolytic anaemia or haemoglobinopathy, the most common of which in this area would be G6PD deficiency.

What are the next steps in advancing this treatment? Any planned future studies or follow-up analyses?

We are currently going through the regulatory approval process with the UK regulator the MHRA. We were granted Innovative Licensing and Access Pathway (ILAP) status which has guided us through early interaction with both NICE – the body that decides whether medicines should be available on the National Health Service. As a company based in Scotland, we are going through the UK regulatory process in the first instance.

While this process is ongoing, we are also currently running a safety study in the United Arab Emirates and also have a long-standing Compassionate Use Program for both previous study patients and de novo requests.

A successful market launch, bringing an oral treatment for this devastating disease that impacts millions worldwide, would clearly be a huge personal achievement for everyone in the company. But bigger than that is the opportunity it would give us to build upon our research to offer even more hope for those suffering from other neurological conditions.

Transcript edited for clarity.