Latest Alzheimer’s investigative drug shows no improvement in cognitive decline


By Alzheimer's Prevention Bulletin

Roche and Genentech recently announced that their anti-amyloid investigative drug did not meet the trial’s primary endpoint of slowing cognitive decline. The drug is one of several amyloid targeting treatments currently in trials.

Several amyloid clearing drugs for the treatment of Alzheimer’s disease are currently in trials in the United States and around the world. In November, one of these investigational drugs was shown to be ineffective at meeting it’s therapeutic goals.

Roche and Genentech announced negative results from two Phase 3 trials of gantenerumab, an anti-amyloid treatment for Alzheimer’s disease. The pharmaceutical companies stated in their press release that the drug failed to slow cognitive decline and removed less amyloid plaque from the brain than expected.

The GRADUATE I and GRADUATE II studies were investigating gantenerumab in people with mild cognitive impairment due to Alzheimer’s and mild Alzheimer’s dementia. While there were numerical differences between drug and placebo arms for measures of cognitive decline and removal of amyloid plaque from the brain, the effects were not statistically significant. The results from these trials along with those from other anti-amyloid treatments suggest that there is a relationship between the amount of lowering of amyloid and clinical outcomes. Although gantenerumab did reduce the amount of amyloid in the brain, it was not enough to slow cognitive decline.

The pharmaceutical companies have gathered high quality, clear and comprehensive data from the trial which they will share with the scientific community. It is their hope that this data, along with data from other trials, can inform future studies in Alzheimer’s disease. Roche is developing a version of gantenerumab, called trontinemab, that uses “brain shuttle” technology” to get the drug across the blood-brain barrier and boost the amount of the active ingredient within the brain.

While these results are disappointing, the data from the gantenerumab program should reveal more insights into the complex relationship between the removal of beta-amyloid plaque and

its impact on slowing cognitive decline. Gantenerumab is one of several drugs currently in trials that treats Alzheimer’s disease by removing plaque to reduce cognitive decline.

The drug lecanemab recently reported positive results showing a 27% reduction in clinical cognitive decline as compared to placebo after 18 months of treatment. Eli Lilly is currently in Phase 3 trials with an anti-amyloid drug, donanemab. Aduhelm is another anti-amyloid drug approved by the FDA in June 2021.

Data from both the lecanemab and gantenerumab trials were presented at the Clinical Trials in Alzheimer’s Disease Conference in November 2022. Alzheimer’s researchers believe it will be important to compare data from these anti-amyloid drug trials to learn why some treatments work and others do not.

More than 140 investigational drugs are currently in trials for Alzheimer’s disease. Researchers remain hopeful that a combination of these medications will help address the symptoms and the prevention of Alzheimer’s for the millions of people and their families afflicted with this disease. To find a study near you, please visit our Find a Study page.