Medication for Dementia - Aducanumab
This week we’ll jump into a newly approved medication for Alzheimer’s disease, Aducanumab. This approval occurred on June 7th, 18 years since the last medication approval for Alzheimer’s disease. The decision may be one of the most controversial approvals made by the FDA and has made for plenty of discussion.
First, a quick reminder that Alzheimer’s disease is the most common cause of dementia, somewhere between 60-80%. The underlying cause is thought to be due to “plaques and tangles,” where the plaques are caused by a specific protein called amyloid. This is called the “amyloid hypothesis,” and is based on post-mortem studies of persons that have passed away from Alzheimer’s disease in whom these plaques are seen in the brain; and that the gene for the Amyloid Precursor Protein, the protein that becomes amyloid, is located on chromosome 21 and persons with Trisomy 21, also known as Down Syndrome, can have disease manifestations similar to Alzheimer’s disease at a much earlier age than average. There is a correlation in these plaques and Alzheimer’s disease, but there has never been anything to prove causality.
The drug, aducanumab, is a monoclonal antibody. These have received a lot of press recently due to CV-19. The treatments given for CV-19 consist of monoclonal antibody cocktails. A simple way to think of these medications is that they are lab made proteins that are designed to prevent a very specific action from occurring in the body. In CV-19 they are made to prevent the virus from infecting cells. Aducanumab specifically binds the amyloid protein and marks it for “removal” by certain cells, and does result in decreased amounts of amyloid in the brain.
If the amyloid hypothesis is correct, then this decrease in amyloid in the brain should treat Alzheimer’s disease. Unfortunately aducanumab was put through two clinical trials and only showed a small slowing in Alzheimer’s disease in one of the two. The other was stopped early due to “futility,” meaning the drug did not slow down disease progression. In both trials, there was a reduction of amyloid noticed in the brains of participants.
This is where the controversy is centered. The FDA has approved a very expensive medication ($56,000 per year for the medicine alone, and tens of thousands of extra dollars for monitoring) that has not proven to be useful. Three experts have resigned from an FDA advisory committee because of this decision. The door is now open and precedent set for medications of uncertain benefit and based on tenuous hypotheses to be approved. The cost of this medication along with the false hope that comes with it will devastate families facing Alzheimer’s disease.
Key Points:
Aducanumab is the first FDA approved medication for treatment of Alzheimer’s disease in 18 years
There is significant controversy surrounding the approval of aducanumab
