Authors: Sharon Salt, Editor
In March 2019, a decision to discontinue the global Phase III trials of aducanumab for Alzheimer’s disease (AD) shook the field. Little to no information was provided about why the compound failed at the time – did it not lower plaque burden? Was there too much measurement variability? The answer remained uncertain.
However, in a big turn of events, Biogen (MA, USA) and Eisai (Tokyo, Japan) decided in October 2019 that they were going to pursue regulatory approval for the drug after analysis with a larger data set indicated that there was a reduction in clinical decline compared with the control group in the EMERGE trial, but not ENGAGE.
Once again, very little information was provided about the two trials – for example, what was different between them? Why did the ENGAGE trial fail? At the Clinical Trials on Alzheimer’s Disease Congress (4–7 December, San Diego, CA, USA) yesterday, Biogen presented detailed data on this to illustrate that the difference in the results were due to the effects of a late change that the company made to their studies – that is, allowing study participants to receive higher doses of the compound.
EMERGE versus ENGAGE
STAT news reported that within the main study analysis for EMERGE, individuals receiving a low dose of aducanumab had a rate of decline on the CDR-SB by 14%, whereas individuals on the low dose of aducanumab had a score of 23%. According to the presented data, only the result from the high-dose group was statistically significant. In comparison with the ENGAGE trial, the CDR-SB score in individuals receiving the low dose was reported to be a decrease of 12%, whereas the high-dose group had an increase of 2% .