TauRx Therapeutics Management Ltd today announced results from its Phase III LUCIDITY trial evaluating the efficacy and safety of hydromethylthionine mesylate (HMTM) in the treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) have been published in The Journal of Prevention of Alzheimer's Disease.
The trial reports that participants with MCI who received HMTM 16 mg/day experienced statistically significant cognitive improvement over 18 months, with no significant cognitive or functional decline observed over a period of two years.
Professor Claude Wischik, TauRx Co-Founder and Chairman, who is lead author of the paper, said: “These results show HMTM has the potential to offer an accessible oral treatment option with a benign safety profile which could be delivered with minimal patient or physician burden.
“The study also found starting HMTM treatment early in the disease process is important for preservation of cognitive function and that it impacts the underlying disease process in AD.
“This study confirms results from earlier trials showing that HMTM has a benign safety profile, with headache (1.5%) and diarrhoea (1.2%) reported as the most frequent adverse effects.”
The trial evaluated the safety and efficacy of HMTM in 598 participants with MCI and mild to moderate dementia due to Alzheimer’s disease (AD). All participants were amyloid β-PET positive, with 44% (263) meeting the clinical criteria for MCI due to Alzheimer’s disease, and 56% (335) diagnosed with mild to moderate dementia due to AD.
The paper, entitled Clinical, imaging and blood biomarker outcomes in a Phase 3 clinical trial of tau aggregation inhibitor hydromethylthionine mesylate in mild cognitive impairment and mild to moderate dementia due to Alzheimer’s disease, reports on the trial which was conducted at 82 sites across Canada, the European Union, United Kingdom, and United States.
It compared 16 mg/day and 8 mg/day doses of HMTM with 4 mg twice weekly doses of methylthioninium chloride (MTC). MTC was required as a urinary colourant to preserve blinding due to possible urinary discolouration caused by HMTM.
In the trial, HMTM and MTC were compared on cognitive and functional endpoints for the first 52 weeks followed by all patients receiving HMTM 16 mg/day to 104 weeks in a modified delayed-start trial design. Unexpected initial symptomatic activity in the MTC arm interfered with the intended primary outcome analyses at 52 weeks, but not with longer-term outcomes in participants with MCI.
MCI participants receiving HMTM 16 mg/day showed statistically significant differences in cognitive decline (ADAS-cog13) at 78 weeks and 104 weeks in analyses specified prior to the 104-week database lock. Those starting HMTM 16 mg/day after a 52-week delay could not catch up with those starting earlier due to ongoing neurodegeneration during the first 52 weeks in those receiving MTC.
The benefit of HMTM 16 mg/day has been confirmed in a further study utilising closely matched external placebo arm cases from a well-documented trial database to provide true placebo controls not confounded by the blinding problem.
In the early start MCI group receiving HMTM 16 mg/day, statistically significant cognitive improvement over baseline score was sustained for 78 weeks, with no significant cognitive or functional decline over 104 weeks. There was a significant reduction in progression of neurodegeneration measured by NfL change in blood at 52 weeks in both the whole and MCI populations. This was consistent with significant reductions in progression of brain atrophy in scans at 52 and 104 weeks, and a reduction in progression of tau pathology (measured by pTau217 change in blood) in MCI.
The study confirms the results from earlier trials showing that 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).
