TauRx misses primary endpoints in Alzheimer’s combo PhIII trial

The tau theory in Alzheimer’s disease (AD) took a hit today after TauRx, one of the leading companies researching this hypothesis, saw its drug when used with others fail to hit its primary co-endpoints in helping cognition--but there was a small ray of hope that the treatment could work better on its own.

The data, presented today at the Alzheimer’s Association International Conference (AAIC 2016) in Toronto, Canada, showed the biotech’s leuco-methylthioninium-bis(hydromethanesulfonate), also known as LMTX, could not best placebo when used in combination with another marketed Alzheimer’s drug, such as donepezil (Aricept).

Specifically, the 15-month double-blind, placebo-controlled Phase III trial saw the drug used in 891 people (62% female) with probable Alzheimer’s, with already-approved Alzheimer’s treatments being taken by 85% of study participants.

Participants were randomized to receive oral LMTX at doses of 150 mg or 250 mg/day or control (containing LMTX 8 mg/day, to maintain blinding).

Its primary targets were change from baseline on standard measures of cognition and function using the Alzheimer’s Disease Assessment Scale cognitive subscale and Alzheimer’s Disease Cooperative Study-Activities of Daily Living.

These were both, however, missed in the Phase III trial.

In the 15% who took the drug on its own, however, there was some more positive news, as there was a statistically significant benefit on the cognitive and functional outcomes, and brain atrophy measured by MRI, in this subgroup.

This was also the first time brain atrophy was improved in an Alzheimer’s study, according to the Singapore biotech, which also has a base in Scotland.

However, further, larger trials will be needed to confirm whether the candidate can on its own improve cognition.

Serge Gauthier, a professor in the departments of neurology and neurosurgery, psychiatry and medicine at McGill University and first author on the study abstract, said on a call about the results this morning that the trial was “more complicated than we thought, but monotherapy does appear to be the way forward in the future. There may have been pharmacological interactions, but we are not sure [with other Alzheimer’s drugs], but this will inform future trial designs for these types of studies.”

But another investigator working on a TauRx trial said on the same call that he was “more disappointed than not” by the results. “Primary outcomes are exactly that,” he said: “They are primary. They are only thing that really counts, but it did not show any benefits. To not hit that is very disappointing.”

Maria Carrillo, Alzheimer’s Association chief science officer, said in a statement: “The results of this Phase III trial are interesting but also complex, and it will take time for the field to determine what they mean.

“The small number of participants receiving the study drug as monotherapy raises very important questions. Additional research is needed to help us understand these findings so that more and better Alzheimer’s therapies can be created and effectively tested.”

This may also hit the biotech’s hopes of a listing on the Nasdaq, something it has previously said it was looking to do in 2017. The biotech has been much hyped over the years, with research in one way or another for a form of this target going back about 30 years. Last October, it raised $135 million to help it run its late-stage program.

It could also damage the tau theory, which sees the onset of the disease to fibrillary tangles called tau protein. Neurofibrillary tangles group in an insoluble form in neurons, affecting normal neuronal functions.

This is separate to the more popular area of research--but one also beset by failures over the past decade--called the amyloid theory, which believes a buildup and spread of this protein causes the memory-wasting disease.

A drug that is disease-modifying in AD could be worth more than $10 billion a year, but TauRx follows the likes of Pfizer ($PFE), Eli Lilly ($LLY), Biogen ($BIIB) and many others in posting weak data from its primary endpoints. Over the past 10 years, around 99% of all AD trials are believed to have failed.

- check out the release from TauRx

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