Good news and bad news for Aduhelm this week

I was interested to see the report from the Clinical Trials on Alzheimer’s Disease conference held in Boston last week demonstrating a reduction of a blood marker for neurofibrillary tangles in the brain, p-tau 181, in patients receiving Aduhelm in the ENGAGE and EMERGE trials compared to those receiving placebo. There also was a significant correlation of p-tau 181 levels with PET amyloid and cognition.  What this adds to the data released previously is a positive effect on another Alzheimer’s biomarker, the abnormal tau found in the neurofibrillary tangles. This is good news and lends support to the hypothesis that lowering amyloid levels in the brain can slow progression of Alzheimer’s disease.  I looked closely at Biogen’s press release on the data because the headlines I saw seemed to imply that subjects receiving Aduhelm had lowering of their own p-tau 181 levels.  That would be surprising because it would imply that a medication directed at beta-amyloid could reduce the downstream tau in the neurofibrillary tangles.  That is not what the data showed.  The group that received Aduhelm had lower levels of tau than the group that received placebo.  In other words, there was evidence suggesting decreased progression of disease in treated patients but no evidence of removal of neurofibrillary tangles already present.  This is an important distinction. Anti-amyloid drugs at best may slow progression of Alzheimer’s, but we can’t expect them to reverse damage that has already occurred. Still, I think this is good news that supports the hypothesis that attacking brain amyloid may slow the cognitive decline of Alzheimer’s disease.

The bad news was the first reported death from brain edema apparently caused by Aduhelm. According to an article in Reuters (I couldn’t find a press release from Biogen), Biogen is investigating the death of a 75-year-old man who developed brain edema and died after starting treatment with Aduhelm. Brain swelling and tiny hemorrhages called ARIA (amyloid-related imaging abnormalities) are a common side effect of Aduhelm and similar drugs, but usually they are mild, reversable and cause mild or no symptoms.  Serious side effects occur in less than 2% of subjects, but even these can usually be managed successfully. As I described in Tattoo, I had severe brain swelling and microhemorrhages after just four doses of Aduhelm during the ENGAGE trial requiring two days of ICU care, but I fully recovered over the next few months. The point is this: Aduhelm has side effects that can rarely be severe and life threatening. In my opinion, the drug should be given only by doctors knowledgeable in managing these potentially catastrophic reactions.