Phase II results of the first clinical trial of a tau aggregation inhibitor (TAI) for Alzheimer's disease were published last month in the Journal of Alzheimer's Disease, with Singapore-based TauRx Pharmaceuticals saying it was an important milestone as it moves to report top line results from a Phase III study in 2016.
The Phase II work "provided the basis and rationale for subsequent Phase III clinical trials of a TAI in AD currently in progress" and showed "evidence of arrest of decline."
In a research field littered with failure, the release shows the determination of company founder Claude Wischik to insist that more than a decade working on a drug that would inhibit the aggregation of tau tangles in the brain will pay off in a way that major drug companies have missed repeatedly and spectacularly.
But despite little buzz from the key opinion leaders in the field, or indeed any suggestion that a blockbuster treatment is around the corner that could potentially dwarf the best-selling drug of all time, Lipitor, Wischik soldiers on.
He did it by raising more than S$300 million over that period from small investors mostly from Southeast Asia and medical backgrounds, but also from Singapore's Temasek and S$120 million from Malaysian casino and resort operator Genting Group.
Of course the stakes are high. A treatment for Alzheimer's disease to delay onset has not only been elusive, but even understanding disease progression and diagnosing it correctly remains a hurdle as demand for acute care is surging as many countries face a steady increase in aging populations.
Wischik said his focus is on the tangle pathology originally discovered by Alois Alzheimer, not on beta amyloid that firms such as Eli Lilly ($LLY) and Pfizer ($PFE) have explored aggressively. His research suggests one way to treat the symptoms is by dissolving paired helical filaments with pharmaceutically viable compounds acting as TAIs, to delay disease onset.
Indeed, he reported in 1996 that the chemical substance methylthioninium (MT), and commonly known as "methylene blue", used in medicine for the last 100 years, dissolves tangle filaments isolated from the human brain by selectively blocking a critical step in the process required to form the rogue filaments.
But there was a problem in the use of the drug in Phase II that the release says has been solved.
"TauRx scientists discovered that MTC suffers from dose-dependent impairment in absorption when taken with food. This is due to the fact that the oxidized MT+ form needs to be actively converted to the reduced LMT form in the gut before it can be absorbed as LMT. In other words, MTC is a pro-drug for LMT, and food interferes with the conversion and absorption process. Since MTC was given with food in the Phase II trial to maximize tolerability for patients, only 109 mg/day of the intended 228-mg dose was available for absorption. Therefore, the minimum effective dose of 138 mg/day identified in the trial was simply the highest available dose tested."
The company said a new version in Phase III, denoted LMTX for now, is better absorbed and tolerated than MTC.
"This has enabled Phase III trials to test whether an even higher level of efficacy can be achieved without significant loss of tolerability and safety," the release said.
"These trials are now fully recruited and the first results are expected in the first half of 2016. If the Phase III clinical trials confirm a level of efficacy and safety similar to that seen in the Phase II trial reported in the Journal of Alzheimer's Disease, a treatment targeting the Tau aggregation pathology of AD could be on the market as early as 2017."
- here's the TauRx release
- and more trial info