TauRx Therapeutics’ experimental Alzheimer’s disease treatment LMTX may slow cognitive decline in patients at doses as low as 4 mg — but only when used without other Alzheimer’s drugs — a recent report shows.
The findings support data from an earlier Phase 3 trial, which also studied much higher doses of the drug, and have opened up for a study comparing the low dose to a placebo, the company reported.
The study reporting the insights, “Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer’s Disease: Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial,” was published online in the Journal of Alzheimer’s Disease.
In 2016, TauRx reported results from its initial Phase 3 trial (NCT01689246) in the journal The Lancet. The study had explored the effect of two high doses twice daily, 75 mg and 125 mg, of LMTX in patients with mild to moderate Alzheimer’s disease.
Since the drug is known to cause urine and feces to take on an abnormal color, researchers used a 4 mg dose twice a day as a control, instead of using a placebo. Patients in the trial were allowed to take other Alzheimer’s drugs, such as cholinesterase inhibitors or memantine.
The analysis revealed no statistically significant benefit of the higher doses when taken together with other medications, but when researchers looked at the group of patients who took LMTX as the sole treatment, another picture emerged.
The higher doses in people taking LMTX appeared to slow cognitive decline compared to the lower dose — used both on its own and as an add-on. But researchers also detected that the lower dose, when used on its own, was linked to better outcomes than when used together with other medications.
The insights allowed TauRx to include the analysis in its second Phase 3 trial of the drug. The study, called TRx-237-005 (NCT01689233), noted the same thing. Patients taking LMTX as the only treatment ( 4 mg or 100 mg twice a day) had a slower cognitive decline than patients combining the drug with other medications — a finding that suggested the higher doses were unnecessary.
In addition to improved measures of cognitive decline, patients on LMTX monotherapy slowed their rate of brain tissue wasting to rates seen in healthy older adults and improved their brain blood glucose use. Meanwhile, people using LMTX as an add-on continued having brain tissue loss at a rate typical for Alzheimer’s patients.
Since both Phase 3 trials allowed patients to keep taking their Alzheimer’s drugs, the number of included patients that had LMTX as the sole treatment in the two studies was small, Claude Wischik, a professor at Aberdeen University and executive chairman of TauRx, explained in a press release.
But finding the same pattern of results in both studies makes it unlikely to be a chance finding, he added.
Researchers also excluded the possibility that other factors — including drop-out rates and geographical region — influenced the results.
“Although these results come from non-randomised cohort analyses, a number of things point to real treatment effects and not just differences between patients taking or not taking the standard treatments,” said Wischik and added that researchers are now beginning to understand how the presence of the other Alzheimer’s treatments may impact the effects of LMTX — knowledge gained from animal studies.
LMTX is a compound that prevents the aggregation of tau protein, which, along with amyloid-beta, is a key finding in the brains of Alzheimer’s patients.
“These highly significant results support further validation of tau-based therapy in Alzheimer’s disease,” said George Perry, dean of sciences at the University of Texas at San Antonio and editor-in-chief of the Journal of Alzheimer’s Disease.
TauRx will launch additional trials exploring LMTX soon.