Another experimental Alzheimer’s disease treatment has failed in a late-stage study.
Another experimental Alzheimer’s disease treatment has failed in a late-stage study. Takeda Pharmaceutical and development partner Zinfandel Pharmaceuticals have pulled the plug on their five-year Phase III TOMMORROW trial following an interim analysis.
The two companies said the planned futility analysis showed an inadequate treatment effect with the investigational drug pioglitazone 0.8 mg SR in delaying the onset of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD). The TOMMORROW trial was investigating the genetic-based biomarker risk assignment algorithm (BRAA) as well as evaluating the safety and efficacy of the investigational drug. There were no safety concerns, the companies said. The companies were investigating if the drug could delay the onset of MCI due to Alzheimer’s in cognitively normal individuals projected to be at high risk, as determined by the BRAA. When the companies initiated the trial in 2013 they noted the risk assignment algorithm is comprised of apolipoprotein E (APOE) and TOMM40 genotypes and age. Age and APOE genotype have previously been shown to indicate elevated risk of AD. The addition of TOMM40 is hypothesized to further refine the risk determination, the companies said.
Emiliangelo Ratti, head of Takeda’s Neuroscience Therapeutic Area, said the two companies will analyze the data, which includes performance of a genetic-based biomarker risk assignment algorithm. Ratti said the companies hope the data will “ultimately help in the global fight” against Alzheimer’s disease. Results from the TOMMORROW trial will be presented at a future scientific meeting and efforts will be made to share the primary data with the scientific community, Takeda said in a statement.
Ann Saunders, chief executive officer of Durham, N.C.-based Zinfandel, said the Phase III trial will provide invaluable clinical data that will provide “valuable insights into the earliest stages of the AD process and contribute to easing the burden of AD.”
Despite this failure, Takeda said it remains committed to investigating Alzheimer’s therapies. That commitment was seen at the start of the year with a collaborative agreement with Denali Therapeutics for three Alzheimer’s disease programs in a deal that could be worth up to $1 billion when regulatory and clinical milestones are factored into the equation. The companies did not divulge much information on the three programs, but they jointly said the ATV technology will enhance blood-brain barrier penetration in Alzheimer’s patients.
Alzheimer’s and other forms of dementia are a growing healthcare concern. In the United States, Alzheimer’s disease is the sixth-leading cause of death across all ages and the fifth-leading cause of death in people over 65 years of age. By 2050, the number of global patients is expected to hit 131.5 million.
To say it’s been difficult to develop a treatment for Alzheimer’s would be a tremendous understatement. Multiple companies have seen clinical failures. In September, Axovant reported its Phase III trial testing intepirdine in Alzheimer’s patients failed to distinguish itself against placebo. Earlier this month, Pfizer said it was abandoning research and development into new neuroscience development, including Alzheimer’s and Parkinson’s disease.
This week Eli Lilly published data from its failed EXPEDITION3 trial that casts doubt on the amyloid beta plaque theory of Alzheimer’s. In an article published in the New England Journal of Medicine, Lilly said it could not validate findings from earlier trials that its drug solanezumab could slow down cognitive decline.
