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Gantenerumab improved markers of disease in rare, inherited form of Alzheimer’s disease

Further analysis of data from an international trial of two investigational drugs in people in the early stages of a rare, inherited form of Alzheimer’s disease has demonstrated that one of the drugs had a positive impact on biomarkers of the disease.

The study ( Identifier: NCT01760005) is a phase 2/3 trial led by Washington University School of Medicine in St. Louis through its Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU). The trial separately evaluated the effects of two drugs – solanezumab, made by Eli Lilly and Co., and gantenerumab, made by Roche – known as Genentech in the United States – in people with a rare, inherited, early-onset form of Alzheimer’s called dominantly inherited Alzheimer’s disease or autosomal dominant Alzheimer’s disease. Such people experience declines in memory and thinking starting in their 50s, 40s or even 30s.

The primary endpoint of the study was a slowing of cognitive decline as measured by multiple tests of thinking and memory. A February 10 press release issued by Washington University School of Medicine announced that an initial analysis indicated neither drug met the primary outcome nor demonstrated cognitive benefit. However, further analyses of trial data for gantenerumab demonstrated improvement in biomarkers of disease activity and progression, including measures of tauopathy and neurodegeneration. Gantenerumab reduced the pathology of amyloid plaques, reduced soluble cerebrospinal fluid (CSF) tau and phospho-tau and slowed increases in the neurofilament light chain (believed to be a marker of neurodegeneration) when compared to placebo.

The DIAN-TU thinks these findings are important indicators that gantenerumab can affect the biological course of the disease and have launched a multiyear exploratory open label extension in collaboration with Roche to continue studying the effects of gantenerumab in this rare form of Alzheimer’s. These findings were presented to the scientific community on April 2, 2020 during the Advances in Alzheimer’s and Parkinson’s Therapies annual meeting. Additional findings will be presented at the upcoming Alzheimer’s Association International Conference in July.

“By continuing the study of gantenerumab through an exploratory open label extension, we will determine whether the drug can completely remove amyloid plaques from the brain, and by doing so, determine if other pathologies related to disease progression (for example, neurodegeneration) are substantially improved as well,” said principal investigator Randall J. Bateman, MD, director of DIAN-TU and the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University. “We will also track memory and thinking, and how long it takes for the disease to progress to dementia.”

The goals of the exploratory open label extension are:

  • To allow participants, who have committed 4 to 7 years to the double‐blind treatment period of the study, to continue or begin to receive gantenerumab, which improves critical biological markers of their progressive disease;
  • To determine if continued treatment with gantenerumab at its target dose can result in complete removal of brain amyloid;
  • To investigate which non‐amyloid related downstream biological measures (e.g. tau and neurodegeneration) can be improved or normalized with complete removal of amyloid at different stages of disease; and
  • To investigate the relationship of these biological measures with cognitive and clinical findings.

Individuals originally enrolled in the DIAN-TU trial of solanezumab and gantenerumab are potentially eligible for enrollment in the exploratory open label extension. Eligible trial participants will take the active form of the drug without placebo. The exploratory open label extension allows active drug to be given to all participants and follow them over time.  Since everyone in the extension will receive active drug, only people who carry the early-onset Alzheimer’s disease mutation will be able to participate.

The DIAN-TU is committed to starting the open label extension as soon as possible and is working with stakeholders to address challenges related to COVID-19 and minimize delays to initiation. Please visit the DIAN website to see an updated list of frequently asked questions about the exploratory open label extension.

A discussion about the exploratory open label extension by top researchers can be found on the Alzforum website,

The DIAN-TU is excited to offer this opportunity and looks forward to learning more about long-term effects of gantenerumab, removing amyloid plaques and the impact on Alzheimer’s disease. In addition, the DIAN-TU continues to expand its platform to investigate new drugs with novel biomarker targets of Alzheimer’s, such as tau-based therapies.

The DIAN-TU trial platform is supported by the Alzheimer’s Association, the National Institute on Aging of the National Institutes of Health (NIH U01AG042791, NIH R01AG046179, NIH R01AG053267 – PI RJ Bateman; NIH U01AG059798 – PI EM McDade), GHR Foundation, FBRI, Eli Lilly and Co., Roche, Janssen, and Avid Radiopharmaceuticals. More information about the trial can be found on ( Identifier NCT01760005) and on Washington University’s Dominantly Inherited Alzheimer Network website.


Categories: DIAN-TU Announcement