A drug that was noted for its potential as an Alzheimer's treatment but was discarded following clinical trial failures has demonstrated new efficacy. While it showed no remarkable effects in treating Alzheimer's, it is effective in preventing Alzheimer's in high-risk groups.
Researchers at the University of Washington School of Medicine disclosed clinical trial results on the preventive effects of the Alzheimer’s drug candidate 'gantenerumab' from Roche in the international journal 'Lancet Neurology' on the 20th. Gantenerumab's development was halted in 2022 after its therapeutic efficacy was not confirmed in clinical trials involving patients with mild Alzheimer’s disease.
Gantenerumab is an antibody protein that binds to amyloid beta proteins. Amyloid beta is originally a protein that protects neurons, but when it detaches from cells and forms clumps, it deteriorates the function of neurons. There are varying opinions in the academic community regarding whether amyloid beta clumps are a direct cause of Alzheimer’s or one of its symptoms, but it is already well-known that amyloid beta clumps trigger the symptoms of Alzheimer’s.
Gantenerumab gained significant attention as Roche developed it as an Alzheimer’s treatment. However, no therapeutic effects were confirmed in a global Phase 3 trial involving about 2,000 patients with mild Alzheimer’s disease. At that time, patients were administered gantenerumab for two years, but the cognitive function improvement effect was limited to 6-8%, which is not a statistically significant difference compared to untreated patients.
Researchers at the University of Washington believed that even if gantenerumab cannot remove already formed amyloid beta clumps, it may be useful in preventing Alzheimer’s if it can prevent the formation of clumps. They included 73 participants in the clinical trial who do not have Alzheimer’s but produce amyloid beta excessively in the brain due to genetic abnormalities. These individuals belong to a high-risk group for Alzheimer's disease.
The clinical trial was originally scheduled to take place from 2020 until the end of 2023, but it was prematurely terminated in mid-2023 after Roche abandoned the development of gantenerumab in 2022. However, the trial confirmed some preventive effects of gantenerumab against Alzheimer’s during this period.
Notably, the group of participants who received gantenerumab for the longest duration of eight years showed the best effects. Among the 22 individuals in this group, the probability of developing Alzheimer’s was shown to be reduced by at least 50%. A shorter treatment duration group also confirmed a prevention rate of approximately 21% for Alzheimer’s.
The researchers explained, "Participants who received gantenerumab did not exhibit symptoms even after the predicted onset age of Alzheimer’s, as indicated by family history and genetic analysis, and it appears that the longer the treatment period, the greater the efficacy. "
However, adverse effects appeared to be somewhat higher than in previous clinical trials. Although there were no health-threatening incidents or deaths among participants, two individuals had to stop their gantenerumab treatment due to severe side effects.
The researchers assessed that they were able to confirm the potential for Alzheimer’s prevention through this study. Although only individuals with high-risk genes for Alzheimer’s participated in this clinical trial, they stated that others who may develop Alzheimer’s due to different causes could also benefit from preventive effects.
Randall J. Bateman, a professor emeritus at the University of Washington, noted, "Several clinical trials of a similar nature are being conducted simultaneously; if positive effects are confirmed in these studies as well, it would provide the first clinical evidence that preventing Alzheimer’s is possible."
Researchers are also conducting a clinical trial on Alzheimer’s prevention using 'remternetug,' an Alzheimer’s treatment candidate from the American pharmaceutical company Eli Lilly, alongside gantenerumab. The Phase 3 clinical trial for remternetug is currently underway, and results are expected to be announced within this year.
References
Lancet Neurology (2025), DOI: https://doi.org/10.1016/S1474-4422(25)00024-9