Novel Tau-Targeting Medication for Alzheimer Disease Associated with Sustained Cognitive Benefit
People diagnosed with early Alzheimer disease (AD) who were treated with the oral tau aggregation inhibitor HMTM (hydromethylthionine mesylate; TauRx Pharmaceuticals, Aberdeen, United Kingdom) showed improvements in standard cognitive and functional outcomes according to research presented at the AD/PD 2024 International Conference on Alzheimer’s and Parkinson’s Diseases. According to these new findings from the LUCIDITY clinical trial (NCT03446001), cognitive and functional benefits remained above baseline for 18 months, only returning to baseline at 24 months. Data previously reported in 2023 from this trial showed a 95% reduction in neurofilament light chain (NfL) blood concentrations over 12 months in those treated with HMTM compared with placebo. This reduction in blood NfL correlated with phosphorylated tau at threonine 181 (p-tau181), a biomarker for Alzheimer disease severity.
LUCIDITY was a phase 3, randomized, double-blind, placebo-controlled, 3-arm clinical trial assessing the safety and efficacy of HMTM as a monotherapy for people with AD. The study included 446 people with a diagnosis of AD including probable AD and mild cognitive impairment due to AD (MCI-AD) in the initial 12-month 3-arm portion, with participants receiving either HMTM at 16 mg/day once daily, HMTM at 8 mg/day once daily, or placebo. After 12 months, all participants received HMTM at 16 mg/day for an additional 12 months in a modified delayed-start open-label treatment phase. Cognitive outcomes were measured according to Alzheimer Disease Assessment Scale—Cognitive Subscale (ADAS-Cog). Details of the study design for LUCIDITY were published in The Journal of Prevention of Alzheimer’s Disease.
Participants in the group with early AD treated with HMTM at 16 mg/day showed a significant reduction in transition to the dementia stage of AD compared with participants in the control group. Participants in the control group declined significantly below baseline measures with respect to ADAS-Cog assessment, despite switching to the treatment with HMTM at 16 mg/day after 12 months.
"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," said Professor Claude Wischik, CEO and Executive Chairman of TauRX Pharmaceuticals. "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 profile over 12 months reaching levels sufficient for symptomatic activity even at a very low dose."