Study Results from DIAN-TU Trial Presented at Recent Medical Meeting

New data from the DIAN-TU study, which is testing drugs in people with a rare inherited form of Alzheimer’s disease, shows the value of biomarkers in clinical trials and further validates the need for Alzheimer’s research to focus on diverse drug targets beyond amyloid. Investigators from the Washington University School of Medicine presented the results at the first virtual AAT-AD/PD [International Conference on Alzheimer’s & Parkinson’s Diseases] meeting on April 2.

Investigators reported earlier this year that neither study drug, solanezumab (Eli Lilly and Co.) or gantenerumab (Roche and Genentech), met the primary goal of slowing cognitive decline. But they also collected spinal fluid samples and used an amyloid PET brain scan, to monitor the biological changes associated with treatment.

Investigators measured the levels of four proteins that are implicated in Alzheimer’s disease in the spinal fluid of study participants.  Both drugs reversed abnormal spinal fluid levels of beta amyloid, indicating that they had an effect on their intended amyloid target, and reduced elevated levels of neurofilament light (NfL), a recently validated biomarker that measures neurodegeneration in the brain. In addition, gantenerumab, but not solanezumab, was associated with reductions in two spinal fluid proteins, total tau and phospho-tau, that are thought to reflect neurodegeneration, as well as reductions in the amount of amyloid plaques in the brain measured by PET scan.

“While this study hasn’t given us the holy grail — an effective drug for Alzheimer’s — its innovative design and biomarker findings are moving the field forward,” said Howard Fillit, MD, Founding Executive Director and Chief Science Officer at the Alzheimer’s Drug Discovery Foundation (ADDF. “The positive biomarker results coupled with no clinical effect, that is no significant slowing of cognitive decline — provide further proof that reducing amyloid burden in the brain may not be enough to slow or reverse cognitive and functional decline in Alzheimer’s patients. There must be other processes involved that we need to target therapeutically to have an impact on treating and preventing Alzheimer’s.”

The DIAN-TU study uses an innovative platform trial design, with one placebo control group and simultaneous evaluation of multiple treatment drugs. This will allow investigators to cycle in new drugs for testing without having to develop, validate and gain approval of a new trial design and infrastructure. These efficiencies help trials find meaningful results with fewer patients, fewer patient failures, less time and a greater probability of success than traditional two-arm trials.[1]

We now understand that Alzheimer’s is a complicated disease caused by a range of factors and that a broad approach that moves beyond targeting beta-amyloid is necessary. Like other diseases of aging —cancer, diabetes and heart disease— the answer likely lies in a combination treatment approach that addresses multiple pathways contributing to the disease: misfolded proteins, inflammation, vascular problems, and other aging malfunctions. Trials such as DIAN-TU provide valuable insights that will improve future research.

1. Saville BR and Berry SM. Efficiencies of platform clinical trials: A vision for the future. Clin Trials. 2016;13(3):358-366.