Aducanumab reduces the amount of amyloid plaque in the brain in all three studies: Study 103 (Phase 1), 301 (ENGAGE), and 302 (EMERGE).
Study 302 (EMERGE) significantly reduced cognitive decline over 18 months as measured by CDC-SB, MMSE, ADAS-Cog-13, and ADCS-ADL-MCI. These are instruments that measure cognition and activities of daily living.
Study 301 (ENGAGE) did not reduce cognitive decline over 18 months on any measures of cognition.
Both studies were identical studies, conducted in parallel.
There was no correlation in the amount of amyloid plaque and the subjects performance on the CDR-SB. In order words, subjects who had the most amyloid plaque removed by aducanumab did not have the best cognitive outcome (slowest cognitive decline).
The most concerning side effect was ARIA – Amyloid Related Imaging Abnormalities. This is either swelling (ARIA-E) or bleeding (ARIA-H) in the brain.
About 40% of all patients on high dose aducanumab will develop ARIA. Most will be asymptomatic, but 20% will have symptoms such as headaches and confusion and 15% had enough symptoms they had to stop taking the medication.
Over 18 months, Control subjects (not getting aducanumab) declined 1.74 points on the CDR-SB. That is the equivalent of a 0.1 decline every month. So, after 18 months of treatment, high dose aducanumab slows cognitive decline by 4 months.