TauRx announced preliminary results Thursday from the Phase III LUCIDITY study, showing hydromethylthionine mesylate (HMTM), an inhibitor of tau aggregates, could slow Alzheimer’s disease progression or cognitive decline.
In the overall study sample, 12 months of treatment with HMTM led to an approximately 1-unit improvement in cognition and 1-unit decline in basic functioning scores.
Without any intervention, both metrics are expected to worsen by around five units. HMTM continued to yield cognitive and functional benefits in subgroups of patients with mild cognitive impairment or moderate Alzheimer’s disease.
Enrolling nearly 550 patients, LUCIDITY is a double-blinded and placebo-controlled trial that runs for an initial 12 months, followed by another year of a modified delayed-start open-label treatment phase. HMTM is administered as either 16-mg or 8-mg daily doses at first, while all remaining participants will get 16-mg daily treatments during the trial’s second phase.
LUCIDITY’s co-primary outcomes are cognition and function, as quantified by the Alzheimer’s Disease Assessment Scale and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living.
Because HMTM is known to affect urine color, LUCIDITY also gave placebo participants a urinary discolorant in the form of methylthioninium chloride, dosed at 4 mg twice weekly. However, patients in this arm showed high blood levels of the active drug, enough to breach the threshold of a clinical effect.
“In the absence of a true placebo, the trial as designed could not determine outcomes on primary clinical endpoints relative to a therapeutically inactive placebo as prespecified,” according to a TauRx statement. As a result, LUCIDITY evaluated HMTM’s efficacy using historical but closely matched comparators.
Nevertheless, TauRx found its candidate’s performance compelling enough.
HMTM significantly slowed cognitive decline and brain atrophy compared to the historical controls, indicative of reduced disease progression, the company stated. Moreover, relative to publicly available placebo arms of various trials in Alzheimer’s disease, HMTM conferred meaningful clinical benefits to patients.
HMTM also showed a strong safety profile, with no treatment-related serious adverse events or other amyloid-related imaging anomalies, TauRx reported.
The company plans to use data from LUCIDITY to seek regulatory approval for HMTM in the U.S. and Canada, the filings it expects to submit next year.
A Different Attack on Alzheimer’s Disease
While Biogen and Eisai’s recent Phase III victory with lecanemab sparked hope for the anti-amyloid approach to treating Alzheimer’s disease, experts have urged caution.
HMTM is an oral candidate that targets the other hallmark protein pathology in Alzheimer’s disease: tau. Under healthy circumstances, tau proteins help stabilize neurons and facilitate the transport of neurotransmitters and nutrients. When misfolded, tau fibrils clump and tangle, which disrupts healthy neuronal function.
Tau aggregates are known to be markers of cognitive decline and Alzheimer’s disease progression. In some cases, these clumps have been detected in brains years before the condition arises. HMTM treats Alzheimer’s disease by preventing tau tangles from forming in the first place or by dissolving existing aggregates.
“The field has focused mainly on amyloid as a target for early intervention,” said Claude Wischik, executive chairman and co-founder of TauRx, in a statement. “Our data are consistent with the evidence that Tau pathology begins at least 20 years before clinical symptoms appear and is a viable first-line target for treatment.”
“The availability of an accessible oral treatment which does not require expensive monitoring over routine clinical care opens up an opportunity to intervene before the onset of the cognitive and functional decline that lead to loss of independence,” he added.