At the AD/PD 2025 International Conference on Alzheimer's and Parkinson's Diseases in Vienna, Austria, TauRx Therapeutics presented compelling new analysis from its Phase III LUCIDITY trial, demonstrating significant efficacy of LMTX (hydromethylthionine mesylate) in treating mild cognitive impairment (MCI) and mild-to-moderate Alzheimer's disease.
The data, presented on April 5, 2025, showed that LMTX treatment resulted in an 82% reduction in cognitive decline compared to matched placebo at 18 months, as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog13). This effect was even more pronounced in early Alzheimer's patients, where the reduction increased to 115%.
LMTX is an oral small molecule that works by inhibiting tau protein aggregation and has a secondary symptomatic effect of increasing acetylcholine levels in the hippocampus. The drug is currently in pre-registration in the United Kingdom.
Significant Clinical Benefits Demonstrated
The analysis presented at AD/PD 2025 revealed multiple positive outcomes for patients receiving LMTX at a dosage of 16mg/day for 18 months:
- 35% reduction in brain atrophy progression (measured by whole brain volume) compared to matched placebo
- 77% reduction in global clinical decline (measured by Clinical Dementia Rating-Sum of Boxes) at 24 months
- 71% of LMTX-treated patients maintained or improved their global Clinical Dementia Rating after two years, compared to only 52% for matched placebo
Dr. Claude Wischik, Executive Chairman and Co-Founder of TauRx Therapeutics, commented on the findings: "These results provide further validation of LMTX's potential as a disease-modifying treatment for Alzheimer's disease, targeting the tau protein that is fundamental to disease progression."
Unique Development Challenges
TauRx has faced distinctive challenges in the development of LMTX. Due to the drug's property of causing urinary discoloration, it has not been possible to conduct a traditional placebo-controlled trial where participants remain blind to their treatment arm. Regulatory guidance discouraging the use of a "true placebo" led to the pivotal LUCIDITY trial being designed without a placebo control.
To address this limitation, TauRx conducted an innovative analysis using placebo trial data from contemporary Alzheimer's disease trials available in the Critical Path in Alzheimer's Disease (CPAD) database. Patients from the LUCIDITY trial who received 16mg/day LMTX for 18 months were closely matched to subjects in the CPAD database on multiple measures including age, sex, smoking history, APOE genotype, positive amyloid-PET scan, Clinical Dementia Rating score, and Mini-Mental State Examination score at baseline.
The results presented at AD/PD 2025 were consistent with findings presented at AD/PD 2024 that compared LUCIDITY trial patients with historical matched individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI).
Regulatory Status and Market Potential
TauRx submitted a marketing application for LMTX for the treatment of MCI and mild-moderate Alzheimer's in the UK in July 2024. In December 2024, the company received a request for further information, with a response submitted in February 2025.
If approved, LMTX would become the first orally available disease-modifying therapy for Alzheimer's in the UK. Given that currently approved therapies like Eisai/Biogen's Leqembi (lecanemab) and Eli Lilly's Kisunla (donanemab) are approved but not reimbursed in the UK, LMTX could potentially become the first widely available disease-modifying treatment.
Significantly, LMTX would also be the first approved disease-modifying therapy that targets tau protein rather than amyloid beta.
Advantages Over Current Therapies
LMTX offers several key advantages compared to the two currently approved disease-modifying therapies:
- Oral administration allowing for easy integration into existing care pathways, unlike injectable alternatives
- Benign safety profile with no risk of amyloid-related imaging abnormalities (ARIA), a significant concern with amyloid-targeting therapies
- Potential for broader accessibility due to simpler administration requirements
"The oral formulation of LMTX represents a significant advance in treatment delivery for Alzheimer's patients," said neurologist Dr. Sarah Thompson, who was not involved in the study. "If efficacy is confirmed in real-world settings, this could dramatically improve access to disease-modifying treatment."
Future Outlook
Industry analysts suggest that the success of LMTX will likely depend on clear communication of its efficacy to physicians who may be less familiar with trial results that are not traditionally placebo-controlled. Real-world evidence demonstrating clinically meaningful benefits for patients will play an important role in building confidence among prescribing physicians.
The Alzheimer's disease treatment landscape has seen significant advances in recent years with the approval of amyloid-targeting therapies, but LMTX represents a novel approach by targeting tau pathology, which correlates more closely with cognitive decline in Alzheimer's patients.
With an aging global population and the growing burden of Alzheimer's disease, which affects approximately 55 million people worldwide, the potential approval of an oral disease-modifying therapy could represent a significant step forward in addressing this devastating condition.
