Takeda and partner Zinfandel Pharma have started a phase III trial of pioglitazone in people at risk of developing the symptoms of Alzheimer's disease (AD).
The TOMORROW trial will simultaneously assess a low dose of pioglitazone and a risk-assessment algorithm designed to identify patients at risk of developing mild cognitive impairment (MCI) due to AD by looking at their genetic and clinical profiles.
The algorithm - which assesses the status of the ApoE gene as well as another marker called TOMM40 - has been found to show positive predictive and negative predictive values in the range of 70-80 per cent, which compare favourably with imaging and cerebrospinal fluid-based biomarkers, according to the two companies.
Under the brand name Actos pioglitazone has been on the market for years at a higher dose as a treatment for diabetes, bringing in billions of dollars for Takeda before losing patent protection in 2011.
Earlier studies of pioglitazone in symptomatic AD patients showed only a small benefit from the drug, and Takeda and Zinfandel are now looking at using it earlier in the course of the disease - before symptoms develop - to see if it can delay progression.
Pioglitazone (which is known as AD-4833 as an AD treatment) is thought to work by decreasing inflammation in the brain, unlike most other clinical-stage drug candidates which are designed to interrupt the formation of amyloid plaques.
Serial failures among amyloid-targeting therapies in patients with symptomatic AD - recent examples include Pfizer's bapineuzumab and Lilly's solanezumab and LY2886721- have encouraged researchers to look at treatment in pre-symptomatic, at-risk patients as well as the use of alternative treatment approaches.
Meanwhile, currently-registered drugs such as cholinesterase inhibitors which boost neurotransmitter levels in the brain are palliative at best.
"To date, there have been a number of avenues investigated with the goal of altering the course of Alzheimer's disease but results have been unsuccessful," said Zinfandel's chief executive Allen Roses.
"The potential to identify an individual's risk for developing MCI due to AD warrants further investigation," he added.
In the trial, cognitively normal individuals assessed as low risk will be assigned to placebo, while high risk people will be assigned to either AD-4833 or placebo. The study will enrol around 5,800 people and will complete when 410 cases of MCI are uncovered, which should take around five years.
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