Country for PR: United Kingdom
Contributor: PR Newswire Europe
Thursday, October 06 2022 - 21:00
TauRx Announces Results from Phase 3 Alzheimer's Disease Study, LUCIDITY, Assuring Path for Regulatory Submissions
ABERDEEN, Scotland and SINGAPORE, Oct. 6, 2022 /PRNewswire-AsiaNet/ --

- For people with early Alzheimer's (MCI), HMTM treatment resulted in sustained 
improvement in cognition over pre-treatment baseline, and normalisation of 
brain atrophy to a rate similar to healthy individuals
- For people with mild to moderate Alzheimer's, HMTM stabilised cognition and 
function and reduced rate of brain atrophy compared to historical matched 
individuals with AD
- HMTM is an oral drug with a strong safety profile, having no risk of amyloid 
related imaging abnormalities
- TauRx will present the Phase 3 findings at the Clinical Trials in Alzheimer's 
Disease (CTAD) conference on Wednesday, 30th November 2022, in San Francisco

TauRx Pharmaceuticals Ltd is a global leader in tau-based research in 
Alzheimer's disease (AD). Pathological aggregation of Tau correlates with 
clinical disease severity and brain atrophy. It is a hallmark of the disease 
now generally recognised as an important potential target for treating AD.

Hydromethylthionine mesylate (HMTM) is a potent inhibitor of Tau aggregation 
pathology which is taken orally. The Phase 3 LUCIDITY study compared HMTM 16 
mg/day with methylthioninium chloride (MTC) given at a dose of 4 mg twice 
weekly, the minimum required to prevent bias arising from potential urinary 
discolouration. The study was conducted in 598 patients with AD severity 
ranging from Mild Cognitive Impairment (MCI) through to the moderate stage of 

TauRx has now completed the first 12-month double-blind phase of the trial. The 
second 12-month open label period is ongoing, during which all participants 
receive HMTM 16 mg/day. All participants were required to have a positive 
amyloid-PET scan and not to be taking standard symptomatic treatments for AD.

Of those receiving MTC 4 mg twice weekly, the majority were unexpectedly found 
to have blood levels of active drug above the threshold needed to produce 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. In light of the evidence now 
available, TauRx does not believe that a valid blinded placebo-controlled trial 
of HMTM with clinical endpoints is technically feasible. TauRx has therefore 
analysed the data in terms of the relationship between blood concentration of 
drug and treatment effect, change from pre-treatment baseline, and comparisons 
against historical controls available from closely matched data from the 
Alzheimer's Neuroimaging Initiative (ADNI).

The overall baseline MMSE score was 21 for the study population spanning MCI 
through to moderate disease. There was minimal decline over the first 12 months 
in participants receiving the 16 mg/day dose on both coprimary cognitive and 
functional endpoints (1.3 ADAS-cog11 units and -1.0 ADCS-ADL23 units). The 
expected decline over 12 months in an untreated population would be 
approximately 5 units on both scales.

In the 105 participants with MCI (baseline MMSE score 23) receiving the 16 
mg/day dose, there was statistically significant cognitive improvement of 2 
units over the pre-treatment baseline at 6 months (p=0.0002), 12 months 
(p=0.0391) and 18 months (p=0.0473) on the ADAS-cog13 scale. The mean change on 
the instrumental activities of daily living subscale of ADCS-ADL also remained 
above the pre-treatment baseline at 6, 12 and 18 months.

In the 147 participants with mild to moderate AD (baseline MMSE 20) receiving 
16 mg/day, there was a 2.5 unit cognitive decline in the first 9 months and no 
further decline over the following 9 months. The functional decline on the 
ADCS-ADL scale was -2 units at 12 months and -3 units at 18 months representing 
a reduction in decline of about 75% relative to a published meta-analysis of 
publicly available placebo decline data from historical trials in mild to 
moderate AD.

Statistically significant reductions in disease progression as measured by 
change in cognitive function (p=0.0008) and brain atrophy (p<0.0001) were 
confirmed by comparisons of participants receiving the 16 mg/day dose against 
ADNI subjects who were closest to the study population by age and clinical 
severity. The differences remained statistically significant in both MCI and AD 
subgroups.  As expected, LUCIDITY trial participants with MCI entered the study 
with more brain atrophy than ADNI healthy aging subjects and consistent with 
ADNI MCI subjects. Those treated with HMTM 16 mg/day had a rate of progression 
of brain atrophy that was significantly less than in ADNI MCI subjects 
(p<0.0001) and comparable to that seen in ADNI healthy aging subjects. 

Recent trials that have tested treatments targeting amyloid have been conducted 
in comparable or milder populations than the MCI group in the LUCIDITY trial. 
When HMTM is compared to publicly available placebo decline data from these 
studies as a benchmark, the treatment effects on cognitive and functional 
decline are about three-fold larger over 18 months. The benefit seen with HMTM 
is clinically meaningful for people with Alzheimer's.

The safety profile seen in LUCIDITY remains strong and consistent with earlier 
published HMTM trial data. There were no treatment-related serious adverse 
events or evidence of amyloid related imaging abnormalities (ARIA).
On the outcome of the current data analysis, Professor Claude Wischik, 
Executive Chairman and co-founder of TauRx, explains, "This is the first time 
any treatment has produced evidence of sustained improvement over the 
individual's own pre-treatment baseline lasting 18 months at an early 
clinically detectable stage of AD, and stabilization of disease progression at 
more severe stages. The results in AD confirm published findings from two 
earlier HMTM Phase 3 trials. 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.

"Tau pathology of the disease is now recognized as an important target for 
treatment, and it is encouraging that cognitive improvement is seen at such an 
early stage of the disease with a drug targeting Tau. The field has focused 
mainly on amyloid as a target for early intervention. 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."

To assist with next stages, TauRx has appointed strategic regulatory advisors 
in the UK, US and Canada, alongside naming Dr Richard Stefanacci, an 
established global key opinion leader in Alzheimer's, as Chief Medical Officer. 
Dr Stefanacci is a US-based Internist and fellowship trained Geriatrician who 
is an active physician caring for people with Alzheimer's daily.

Dr Stefanacci commented: "These data support our ability to pursue regulatory 
submissions. We look forward to making a significant difference addressing this 
global unmet need with a medication that is affordable, easy to administer, and 
safe. I'm very pleased to be joining the team and supporting the work we're 
undertaking to achieve our mission of bringing treatments to people affected by 
neurodegenerative diseases caused through protein aggregation – Alzheimer's is 
just the beginning."

On the appointment of Dr Stefanacci, Professor Claude Wischik said, "This is an 
exciting time for TauRx, and we are very pleased to welcome Dr Stefanacci as 
our Chief Medical Officer. His joining the dedicated team at TauRx is testament 
to our science and prospects for the future success of the company in helping 
to transform the lives of people with Alzheimer's and other neurodegenerative 
conditions, as well as the caregivers supporting them."


LUCIDITY is the only late-stage clinical trial specifically targeting the tau 
pathology of Alzheimer's. Aggregation of abnormal tau protein is one of the 
hallmark pathologies.

Additional data analysis is ongoing in relation to the 1-year open label phase 
of the trial, secondary endpoints including MRI volumetric brain scans, and 
exploratory endpoints. A summary of the LUCIDITY study protocol has recently 
been published in The Journal of Prevention of Alzheimer's Disease 


The TauRx group of companies was established in 2002 in Singapore, continuing a 
partnership with the University of Aberdeen, with primary research facilities 
and operation based in Aberdeen, UK. The company has dedicated the past two 
decades to developing treatments and diagnostics for Alzheimer's and other 
neurodegenerative diseases due to protein aggregation pathology.

Alzheimer's dementia is a leading cause of death throughout the world and one 
of the most important public health issues to be addressed globally. TauRx will 
contribute to addressing this unmet need with data from LUCIDITY and pursuit of 
Medicines and Healthcare products Regulatory Agency (MHRA) approval through the 
Innovative Licensing and Access Pathway (ILAP), having been granted an 
Innovation Passport, the first stage of the process, in May this year. 

TauRx plans to submit HMTM for regulatory approval in the US and Canada in 
2023, with other territories to follow, in line with its overall plans to 
commercialise HMTM and pursue clinical trials in other related 
neurodegenerative diseases. 

Through dedicated research programs, it is understood that certain age-related 
factors lead to misfolding and aggregation of tau proteins, and the subsequent 
formation of tau tangles in Alzheimer's. These tangles disrupt and damage 
neuronal function, a process that begins many years before symptoms of dementia 
are seen. Tau pathology has been proven to correlate with the clinical decline 
(loss of memory and ability to care for oneself) commonly seen in people with 
Alzheimer's, establishing it as an important target for treatment. HMTM is a 
tau aggregation inhibitor, which effectively crosses the blood brain barrier to 
target the source of this damaging process.

Source: TauRxPharmaceuticals Ltd