A clinical trial carried by the National Institutes of Health (NIH) American has shown that administering an anti-amyloid antibodies in preventive-the gantenumab, experimental treatment developed by Roche/Genentech-in people predisposed to Alzheimer’s disease could reduce the risk of developing it.
participants included in this trial led by the Knight family Dominantly inherited Alzheimer Network-Trials Unit platform were indeed carrying rare hereditary genetic mutations resulting in an amyloid overproduction in the brain predisposing to an early form of the disease. The test was funded by the Genentech laboratory, Alzheimer’s Association and GHR Foundation; His results are published in The Lancet Neurology (1).
“What we now know is that it is at least possible to delay the appearance of the symptoms of the disease, by eliminating amyloid plaques several years before the symptoms, and to offer patients more healthy life years”comment on the authors in A press release from the University of Washington. “In addition, these results bring new evidence to the amyloid hypothesis of Alzheimer’s disease”. Although the test was limited to people with a certain genetic form, the authors “Hope that the results of the study will shed light on prevention and treatment efforts for all other forms of the disease.”
Initially scheduled for three years, this study extension (see box) was interrupted in mid-2023 following the decision of Roche/Genentech to stop The development of the Gantenumab In November 2022, the data of their Phase 3 Graduate I and II pivotal trials evaluating monoclonal antibodies in people with early symptomatic Alzheimer’s disease that did not reach the main evaluation criterion, namely the slowdown in the clinical decline.
Results to be interpreted with caution
The open extension test included 73 participants with no cognitive decline, or very light, and being between ten and fifteen years before the expected age of the first symptoms of Alzheimer’s disease. Some participants had already been previously treated by Gantenumab as part of the main test and others had received a different anti-amyloid (from the solezumab). In inclusion in the extension trial, patients – regardless of their previous treatment – have received treatment with Ganénérumab.
The authors estimate, from the family history of the participants and the existing data, a reduced risk of developing symptoms of almost 50 %, but only for a subgroup of 22 participants not with cognitive disorders at the start of the study and having received the longest medication (on average eight years). For the group of participants who have received Gentenumab only during the extension, no observable effect on cognitive functions has been observed.
After stopping the Gantenumab, participants who have not yet developed symptoms continued to receive lecanémab, “In the hope that they never develop symptoms”, write the authors. However, the results have not yet been analyzed, pending subsidies by NIH. If there was no internal control group in this test, the authors, however, compared their participants to those of a related study (Dian Observation) which had not received any drug treatment and those of the study Dian-Tu on placebo.
-Although this study does not prove in a conclusive manner that it is possible to delay the appearance of Alzheimer’s disease and that it uses a drug that will probably not be available, the results are promising from a scientific point of view
Pr Tara Spires-Jones from the University of Edinburgh
With the Gantenumab, the authors find arias (imaging anomalies linked to the amyloid) higher than those of the initial clinical trial (30 % against 19 %), which researchers attribute “At the higher doses used during the extension”. Two participants had to stop treatment due to the severity of these anomalies and are currently “Resturbed”. No potentially deadly adverse event has been observed, nor any death, the authors conclude that “A Ganénérumab safety profile similar to that of the initial trial and other clinical trials”.
The absence of a placebo group, the size of the cohort, the short duration of the extension and the failure of the Gentenumab in the Graduate trial are however elements to take into account in the interpretation of the results. The observation of the authors themselves as well as peers in the Science Media Centre, The reduction in the risk evaluated by the authors to 50 % for the group that has been treated the longest must be considered with caution and, in particular, pending long -term observation data.
“I look forward to seeing the results of other treatments administered as part of this test”, Comments Professor Charles Marshall, from the University of London. “Although this study does not prove in a conclusive manner that it is possible to delay the appearance of Alzheimer’s disease and that it uses a drug that will probably not be available, the results are promising from a scientific point of view”, Add the Prof. Tara Spires-Jones of the University of Edinburgh.
R. Bateman et al., The Lancet Neurology, 2025, vol 24, n°4, 316-330
A vast trial on the prevention of Alzheimer’s disease
The population studied comes from the phase 2/3 Knight Family Dian-001 trial, the world’s first global trial of prevention by anti-amyloid drugs (Ganénumab, Solanézumab) of Alzheimer’s disease launched in 2012. This study evaluating the lurerumab alone is an extension test.
