FDA approves aducanumab

Today the FDA approved the use of Biogen’s anti-amyloid monoclonal antibody aducanumab for treating early-stage Alzheimer’s disease.  I have mixed feelings about this approval. As someone living with early-stage Alzheimer’s who participated in the aducanumab clinical trial, I am pleased that patients will now have access to the first drug shown to reduce brain amyloid and modestly slow progression of cognitive impairment in some people with early-stage Alzheimer’s disease. As a retired neurologist, I am less enthusiastic. Two identical trials had different outcomes.  One showed benefit and one did not.  Biogen’s after-the-fact analysis attempted to explain the discrepancy but is statistically fraught.  A strong case can be made that a third trial should have been required before approval. I believe that aducanumab will ultimately be an important tool in fighting Alzheimer’s, but it probably will only work in the earliest stages, before many nerve cells have died, and it may work better or worse on certain subsets of Alzheimer’s disease, for example APOE-4 carriers or those with amyloid in the walls of brain blood vessels (amyloid angiopathy).  We still have a lot to learn.  I worry that aducanumab may be used inappropriately on those with advanced disease for whom it is unlikely to be beneficial.  I also worry that it will become more difficult to recruit research subjects for trials of new therapies that may turn out to be more potent, effectively slowing the push to find better therapies.

I am reminded of the excitement when early in my career tacrine (Cognex), the first acetylcholinesterase inhibitor, was approved in 1993.  This was the very first drug that reduced symptoms of cognitive impairment in some patients with Alzheimer’s. However, liver toxicity was common and limited its use. In 1996 donepezil (Aricept) was approved followed soon after by two other cholinesterase inhibitors.  None of these had the serious liver problems of tacrine and were generally well tolerated.  Tacrine use dwindled and then stopped altogether. Today these three other cholinesterase inhibitors are still widely used. Aducanumab may be the tacrine of today: the first drug of its class with likely effectiveness, but it will almost certainly be joined and possibly replaced by other, more effective drugs in the future.