The results of a clinical trial conducted by scientists at Biogen, was recently published in the journal “Nature.” The trial, which lasted for a year, included 165 early-stage Alzheimer’s patients, identified as prodromal or only mildly affected by the disease. The mini mental state examination (MMSE) upon beginning the trial averaged between 23 and 25 across all test groups. The CDR score (clinical dementia) was 1.0 for the mild group and 0.5 for the prodromal group. Researchers wanted to prove the effectiveness of aducanumab, a monoclonal antibody therapy in clearing amyloid (A-beta) plaque from the brain.
The Trial Format
Subjects were divided into five groups according to dose administered: placebo, 1, 3, 6 and 10 milligrams per kilogram of bodyweight. The degree of amyloid removal in patients mildly affected by Alzheimer’s was quite dramatic. The aducanumab antibody did such an efficient job of cleaning the brain of amyloid that the scans of patients who received the highest doses of the antibody were comparable to patients who were defined as having no amyloid.
The amyloid clearance results were the most dramatic in the group being given the highest dose (10 mg per kilogram) but the adverse reactions were also the most significant in this group. Overall, the higher the dose, the higher the frequency of adverse events. Those receiving the highest dose experienced as much as a 38 percent adverse rate, which if the drug is approved, would present some challenges to patient managers in treatment over long periods. Lower doses resulted in lower frequencies of adverse events, with only 10 percent needing to be discontinued due to side effects.
Slowing of Cognitive Decline Observed
The degree of cognitive decline during the course of the year was very much tied to the dosage, although there was some decline across all the groups. The placebo group showed the most cognitive decline, slightly less than two points measured by the CDR-SB, whereas those receiving the highest dose showed a cognitive decline of slightly more than .05 points. These results carried over to MMSE too. Once again, the placebo group declined more than 2.5 points by the end of the year, and those receiving 10 milligrams declined around 0.5 points. However, MMSE did not seem to be as dependent upon the dose administered because patients receiving 1 mg were not statistically different than those who received 6 milligrams. These results are similar to the performance of Nilvadipine, small molecule also found to reduce levels of amyloid. Nilvadipine is developed by Archer Pharmaceuticals. A major difference, though, is that Nilvadipine is administered once per day orally, whereas aducanumab must be administered by intravenous injection, one dose per month.
In conclusion, the trial results are good news for Biogen’s researchers. The corresponding reduction in cognitive decline with reduction in amyloid gives further support to the theory that reducing amyloid levels in the brain can be a prevention strategy for Alzheimer’s disease.