Aducanumab controversies

Yesterday I participated in a panel discussion regarding recommendations for use of aducanumab, now called by the proprietary name Aduhelm, in the treatment of Alzheimer’s disease. The conference, Dialogue: Current Perspectives on Aducanumab, was sponsored by the Alzheimer’s Association and lasted 4 hours. About 25 Alzheimer’s experts, people living with Alzheimer’s, and a caregiver made up 4 panels.  Over 1500 people from 65 countries tuned in to watch, and the entire conference was recorded and can be viewed as a webinar. I was one of the people living with Alzheimer’s, and I also was asked about my experiences as an aducanumab trial participant, particularly my severe case of ARIA that I describe in detail in Tattoo. It has also been the subject of a case study published in Alzheimer & Dementia last fall.

ARIA, or amyloid-related imaging abnormalities, consist of areas of brain swelling and/or microhemorrhages that occur frequently in subjects receiving aducanumab or other anti-amyloid monoclonal antibodies.  They are more frequent in APOE-4 carriers, and are usually mild, often without any symptoms at all.  They are thought to be caused by the antibody engaging with amyloid in the walls of blood vessels, causing them to leak. Most of the time ARIA resolve quickly and the drug can be restarted.  In 1 or 2% of cases, the ARIA are severe as mine were.  I required ICU care and IV steroids, but I eventually fully recovered with no permanent damage to my brain.

At yesterday’s conference, there seemed to me to be a near consensus that, at least initially, aducanumab be given only by centers already experienced in the administration of these anti-amyloid monoclonal antibodies to ensure that they are used appropriately on patients likely to benefit and that complications can be promptly recognized and treated. There also was considerable concern that the FDA did not limit the use of aducanumab to early-stage Alzheimer’s disease, the only stage that has been tested.  There have been no trials in subjects with advanced disease. In my opinion, there are reasons to believe that it would not be effective and possibly more dangerous to use in this advanced disease subgroup. Equity issues were another important topic of discussion.  Will there be financial barriers for some to receive this medication?

And cost. What about cost? That is worth another post to follow in a few days.