TauRx, based in Aberdeen, Scotland and Singapore, published unexpected results from a pharmacokinetic analysis of the drug hydromethylthionine (LMTM) in Alzheimer’s disease. The research was published in the Journal of Alzheimer’s Disease.
Hydromethylthionine is a WHO-approved, non-proprietary name for a drug previously called LMTM by TauRx. It acts by blocking abnormal accumulation of the tau protein in the brain. Two proteins that accumulate in the brain of Alzheimer’s patients are beta-amyloid and tau. Typically, beta-amyloid occurs earlier in the disease and tau appears later in the disease.
TauRx analyzed the relationship between the treatment doses, blood levels and pharmacological activity of the drug on the brain in more than 1,000 patients with mild-to-moderate Alzheimer’s disease as part of two Phase III global clinical trials. The drug demonstrated concentration-dependent effects on cognitive decline and brain atrophy.
The key findings are that the effects don’t seem to be dependent on the amount of the drug the patients receive.
In several Phase III trials in almost 1,700 patients with mild-to-moderate Alzheimer’s conducted between 2012 and 2016, hydromethylthionine was evaluated at doses of 150 to 250 mg/day compared to a low dose of 8 mg/day. The 8 mg dose was only used as a control to mask the discoloration of urine—it turns it blue—that can occur with the drug.
The company notes, “The study designs were based on the findings from an earlier trial that used a different variant of the drug. Surprisingly, there was no difference between the high doses and the low dose of hydromethylthionine on any of the clinical outcomes in the trials.”
In order to continue exploring the data, the researchers ran a new pharmacokinetic population analysis using data on the plasma concentrations from 1,162 of the patients who were in either of the two completed Phase III trials. They wanted to evaluate how blood levels of LMTM related to the effects on the brain. They utilized a new assay and found that the 8 mg/day hydromethylthionine dose were determined by the blood level. Most of the patients had high enough levels of the drug in their blood at that dose to show meaningful decreases in cognitive decline and brain atrophy.
They concluded that a 16 mg/day dose of the drug would provide all patients with the needed blood levels for maximum drug activity.
“Since we already have a substantial database supporting the safety and tolerability of hydromethylthionine in clinical trials of patients with mild-to-moderate Alzheimer’s disease, the additional results of this analysis have given us the confidence to expand the scope of the new TauRx Lucidity clinical trial to confirm the potential efficacy of the new hydromethylthionine 16 mg/day dose in these types of patients,” said Claude Wischik, executive chairman of TauRx Therapeutics and professor at Aberdeen University.
George Perry, editor-in-chief of the Journal of Alzheimer’s Disease, commented, “The extensive data, experience, and now pharmacokinetics, highlight the potential of hydromethylthionine treatment as an important new avenue forward in Alzheimer’s disease. The clinical benefit and reduction in brain atrophy greatly exceed those reported for other therapeutic routes.”
And the drug is taken orally, which is very different than many of the other investigational therapies in trials. For example, Biogen’s aducanumab, which is currently being evaluated by the U.S. Food and Drug Administration (FDA), is dosed as an infusion.
At this point, hydromethylthionine appears very promising, unusually so in an area where there have been well over 125 clinical trial failures.
“The researchers are aiming to confirm what they have found so far in the placebo-controlled trial that is now ongoing,” said Serge Gauthier, director of the Alzheimer Disease Research Unit at the McGill Center for Studies in Aging. “Hydromethylthionine is the best hope we have right now for a disease-modifying drug acting on the tau pathology associated with Alzheimer’s disease.”
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