Blood Moon 2021
There is a new drug problem that affects older people directly, but really also everyone else. It is the drug that the FDA recently approved, Aducunumab—or Aduhelm, which is its brand name. It is a drug designed to treat Alzheimer’s disease by reducing the size of one of the pathologies associated with the disease, amyloid plaques. The problem is—the drug may have only a minimal benefit.
Many of you have probably been following the controversies around Aduhelm. Two trials by the drug company, Biogen, failed, but then the company conducted a re-analysis and found that one arm of the trial had positive results. The benefits, however, were fairly minimal—a 4 month period during which cognitive decline of participants slowed and some reduction of the amount of amyloid in the brain.
There are three problems here. First is the research is flawed. As two researchers, Aaron Kesselhelm and Jerry Avorn wrote in The New York Times, this was the worst example of how the FDA has been lowering research standards. Conducting a re-analysis can be warranted, because benefits might be found in a specific subset of participants or with some other combination of dosage and other variables, but any time you reanalyze data it increases the possibility of a chance finding. In other words, this type of positive outcome that was found searching through the data needs to be confirmed in a new, independent study, and not used as evidence of efficacy of the drug.
Second, the benefit of the drug is fairly minimal. The cognitive benefits—a slowing of decline for a short period of time—are not as good as results of cognitive stimulation studies conducted in the UK and other European countries or the results of the excellent cognitive rehabilitation training study conducted in the UK by Dr. Linda Clare and her colleagues, who showed that both cognition and brain activity increased with training. As for Aduhelm’s effect on amyloid, other drug trials have shown that reducing the amount of amyloid does not necessarily have clinical benefits for cognition. In other words, removing amyloid does not change the underlying damage done by the disease.
Third, the drug was tested mainly on persons with mild dementia symptoms, but the FDA approved the medication for use by anyone with dementia. It is not obvious that persons with more pronounced symptoms will benefit and the risk of harm is likely to be greater. The medication can result in brain swelling or hemorrhaging. To monitor those risks, patients need regular MRI scans, which could be difficult for persons with more advanced Alzheimer’s disease. Treatment, which consists of a monthly infusion, may also be a challenge for anyone, but particularly persons with significant cognitive decline.
So why was the drug approved? We are sure you have guessed. Money. The FDA was heavily lobbied by the drug companies. According to an analysis in Upshot section of The New York Times, the estimated annual costs for treatment will be $56,000 for the drug alone, plus additional costs for MRIs to monitor for brain swelling. That works out to somewhere between $5.8 billion and $29 billion in annual costs for Medicare and its enrollees. It means that everyone on Medicare will likely face substantial increases in their premiums to pay for this overpriced and largely ineffective drug.
Another factor in the approval was lobbying from the Alzheimer Association and other advocates. The argument they make is that we need to offer hope for people with an Alzheimer diagnosis. Doctors and other health care providers will argue that they need to have something to offer a patient when the diagnosis of Alzheimer is made. This was one of the arguments put forward for the previous Alzheimer medications that were approved. These medications (Aricept, Exelon, and Razadyne) have little or no benefit, other than placebo effects, but at least the side-effects are fairly minimal. We should have compassion for people with Alzheimer’s and other neurodegenerative diseases, but it is not compassionate to make false promises. Instead of filling the coffers of the drug companies, why don’t we for once follow the research, and make the behavioral and cognitive programs that have been shown to be effective more widely available to persons living with dementia and their family members.
Claire, L., et al. (2018). Cognitive rehabilitation, self-management, psychotherapeutic and caregiver support interventions in progressive neurodegenerative conditions: A scoping review. NeuroRehabilitation, DOI:10.3233/NRE-172353.
Katz, J., Kliff, S., & Sanger-Katz, M. New drug could cost the government as much as it spends on NASA. The New York Times, June 23, 2021.
Kesselhim, A., & Avorn, J. The FDA has reached a new low. The New York Times, June 15, 2021.
Woods, B., Aguirre, E., Spector, A. E., & Orrell, M. (2012, Feb). Cognitive
stimulation to improve functioning in people with dementia. Cochrane Database Systematic Review, DOI: 10.1002/14651858.CD005562.