What would you think of a major regulatory body, known for its demanding standards for quality and utility—read integrity—that suddenly abandons its own rules, despite the loud protestations of its own quality advisory committee, and put its imprimatur of approval on a medication that: 1) fails to meet its established endpoints of utility; 2) costs more than $50,000 per year; and 3) has well-documented negative side effects? Not much, I hope. Unfortunately, this is exactly what the U.S. Food and Drug Administration (FDA) recently did with Aducanumab (trade name Aduhelm), a new monthly injection for early Alzheimer’s Disease.

Dementia is the second leading cause of neurologically-mediated lost work years, close behind stroke. Historically, dementias have been divided into distinct categories, the three most common being Alzheimer’s Disease (AD), Lewy Body Disease and multi-infarct dementia. In reality, many persons with dementia have a degree of overlap between these; thus, pure AD—with specific pathological substrates—is typically comorbid with one or more other dementias.

The full causes of AD are still somewhat theoretical, but accumulation of brain amyloid protein has been postulated as a primary cause, “despite > 25 negative past studies testing this hypothesis.” Aducanumab is a monoclonal antibody directed at amyloid. Thus, the underlying rationale for the creation of this treatment is suspect. Add to this the fact that the efficacy trial, with well-defined endpoints for efficacy and futility, was stopped prior to completion, as the treatment met pre-stated futility guidelines. Post-hoc analysis of various studies altered study parameters (changing the rules to change the outcomes) and eliminated “rapid-progressers” from the sample. Only then were outcomes deemed statistically significantly improved. Note that even here the progress of AD is only slowed, and this is not a cure. There is currently no known cure.

The cost is exorbitant. Interestingly, manufacturer Biogen announced it will cut the price in half and offer cost-reduction measures in the face of public outcry. What a bargain! Without proof of efficacy, we will now charge almost $30,000 per year to stoke false hopes.

Ethically, Aducanumab fares poorly with Beauchamp and Childress’s Four Principle Theory:

• Beneficence: There is scant, if any, proven beneficence—other than false hope being offered and the powerful placebo effect of an expensive, injectable medication.
• Maleficence: Maleficence is established—there are serious side effects, including stroke, worsening dementia, nausea, vomiting, MRI changes suggestive of brain damage, and headache. Additionally, even though the dubious positive effects of Aducanumab have been demonstrated only in early disease and for those who are not rapidly progressing, once initiated, patients, families and prescribers will certainly be loathe to discontinue it. Thus, it will be used in patients for whom it is not indicated, despite its known downsides.
• Justice: Justice is highly questionable, as the cost will be prohibitive for many people. For those who can afford the medication via Medicare and insurance products, the cost will be passed on to all of us. Studies performed on this medication did not include significant representation from ethnically diverse populations, bringing into question the applicability of any results to these patients. We don’t know if adverse effects may occur at higher rates or if benefits will differ, as persons of these populations were not adequately studied. Biogen has put financial incentives in place to encourage prescribers to use this medication, creating an obvious conflict of interest, another stimulus to injustice.
• Autonomy: Autonomy, it seems, is the only principle honored by this medication. It certainly does not meet the Hippocratic standard to “First do no harm.” It is relativism at its best. Its efforts to honor autonomy change the physician from a trained professional healer into a technician whose only rule for behavior is the will of the patient.

The American Academy of Neurology recently issued a position statement on conducting “shared decision-making” consent discussions with patients considering the use of Aducanumab. I guess the assumption is that as long as you tell the patients and families all the facts, you will probably be prescribing this. However, there are several problems with this. We know it doesn’t cure the disease. We’re not even sure it will slow AD progression. We know it will be extremely expensive. We know it has some serious side effects. So, with little upside and significant downside, why would any self-respecting physician use this? Because the patient demanded it, and the doctor was afraid of being sued if he/she didn’t prescribe it?

Throw out science. Throw out common sense. If anyone demands this medication for themselves or their family members, and because the FDA has given in with the accelerated approval—it will be prescribed. Doctors who refuse to employ this approved drug will be blamed for abandoning their patients.

Historically, the FDA has often been labeled obstructionist in its staunch unwillingness to approve medications that fail to meet established safety and efficacy standards. It has been known for its conservative high bars. Now it is moving to a “no necessity of proof” standard. If the need for a medication is high, it doesn’t have to be shown to be safe or effective. Lawsuits will follow, and will likely spread against prescribers who are unwilling to write orders for patient-demanded therapies, proven or not. Post-modernism has triumphed. The FDA has lost its moral high ground, and the FDA and medicine itself will suffer.