It’s unique in that it actually compares two different amyloid lowering antibodies in the same trial. The main outcome here was the degree of amyloid lowering at six months. The trial is ongoing and there will be 12-month data reported this summer and there’ll be 18-month data to follow after that. These are patients with early Alzheimer’s disease that either followed the FDA guidelines for aducanumab or the clinical trial criteria for donanemab, and they were both dosed monthly following the titration schedule as outlined either in the prescribing information or trial protocol...
It’s unique in that it actually compares two different amyloid lowering antibodies in the same trial. The main outcome here was the degree of amyloid lowering at six months. The trial is ongoing and there will be 12-month data reported this summer and there’ll be 18-month data to follow after that. These are patients with early Alzheimer’s disease that either followed the FDA guidelines for aducanumab or the clinical trial criteria for donanemab, and they were both dosed monthly following the titration schedule as outlined either in the prescribing information or trial protocol. So that meant there was a slower titration for aducanumab that takes place over six months, where people on the donanemab arm got to the higher dose earlier and had greater exposure to higher dose.
The main outcome, it showed that donanemab had a significantly higher rate of amyloid lowering at six months than aducanumab and that seemed to be relatively safe. The rates of ARIA were similar between the two drugs, so donanemab was able, using that titration scheme, a quicker titration scheme, was able to get more substantial amyloid lowering in a shorter amount of time, and that may be important. Again, the degree of amyloid lowering and the speed of which it’s lowered, and obviously it needs to be done safely, could be important for clinical benefit.
Another thing that was encouraging is that donanemab also showed that there was a significant decrease in p-tau217 in the blood. So, this may be a marker of target engagement and perhaps of treatment response, so we need more information for that. Then aducanumab, we’ll see how the data looks at 12 months when there’s a higher exposure to aducanumab. But at least at six months, donanemab had a greater effect on amyloid lowering and on lowering of p-tau, without causing additional safety concerns. At least in this data set, there were no deaths related to the ARIA.
