TauRx has announced results from a confirmatory study evaluating hydromethylthionine mesylate in participants with mild cognitive impairment and mild to moderate dementia due to Alzheimer’s disease have been published in The Journal of Prevention of Alzheimer's Disease.
The study supports an earlier publication reporting that hydromethylthionine mesylate (HMTM) halted progression of neurodegeneration in Alzheimer’s disease (AD) and that participants with Mild Cognitive Impairment (MCI) who received HMTM 16 mg/day experienced statistically significant cognitive improvement over 18 months. Participants also displayed no evidence of statistically significant cognitive or functional decline over a period of two years.
The newly-reported study compared closely matched external placebo data to show statistically significant treatment effects. The external placebo data were necessary because the control arm for HMTM in the original clinical trial (protocol TRx-237-039) used to maintain blinding with respect to slight urinary colouration by HMTM had some activity and so was not a true placebo.
The latest study compared data from participants who received HMTM 16 mg/day in the original trial with data from matched placebo controls from the FDA-sponsored Critical Path for AD (CPAD) database meeting key inclusion/exclusion criteria (protocol TRx-237-080) as well as with other control populations.
The new paper, titled Assessment of clinical and neuroimaging efficacy of treatment targeting tau pathology in mild cognitive impairment and mild to moderate Alzheimer’s disease with hydromethylthionine mesylate using external control data, reports statistically significant differences relative to three different external control populations. Key analyses suggest that unmeasured confounding is highly unlikely to explain the observed results.
Prof Bjoern Schelter, TauRx’s Chief Analytics Officer, who is lead author of the newly-published paper, said: “The latest results strongly support the effectiveness of HMTM in people living with MCI and mild to moderate dementia due to AD.
“By comparing participants receiving HMTM 16 mg/day with external control populations, we have been able to navigate the blinding problem and so demonstrate consistent and clinically meaningful differences in cognitive decline (ADAS-Cog13) and rate of loss of brain volume at 78 and 104 weeks, as well as a global measure of progression of dementia (CDR-SB) over 104 weeks.
“The latest results are consistent with our earlier report demonstrating that HMTM could have significant treatment effects on neurodegeneration, tau pathology and brain atrophy. The totality of the evidence now available reinforces our belief that HMTM has the potential to offer an accessible oral treatment option which could be delivered safely and with minimal patient/physician burden.”
The original TRx-237-039 (LUCIDITY) trial confirmed HMTM has a benign safety profile, with headache (1.5%) and diarrhoea (1.2%) reported as the most frequent adverse effects at the 16 mg/day dose.
HMTM is an investigational drug and a Marketing Authorisation Application from TauRx Therapeutics Management Ltd is currently being evaluated by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).