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Six million Americans live with Alzheimer’s. Approximately 96 percent of them are over the age of 65 and eligible to receive Medicare.

On June 7, the FDA granted accelerated approval to a landmark anti-amyloid Alzheimer’s treatment. Biogen’s Aduhelm (aducanumab) is a monoclonal antibody which targets a protein, amyloid, that clumps into plaques in the brains of Alzheimer’s patients.

For some, this was cause for celebration; for others, cause for skepticism and upset. Controversy has erupted around the FDA’s decision on Aduhelm. According to many scientists, it is marginally effective at best. Only one of the trial groups outperformed the controls, and then only barely.

Coupled with the efficacy debate is another big question. Aducanumab can never be made widely available due to its prohibitive cost, now standing at $56,000 annually. How will its target audience afford it?

And there’s more to consider. Aducanumab also comes with some potentially risky side effects as plainly laid out below in the a re-print of an essay by Dena Davis, JD PhD, a Fellow at the acclaimed Hastings Center, a bioethics research institute and think tank.

Before discussing affordability and the associated lack of access for a broad population, take a few minutes of time to read her practical and personal assessment of this drug and its small print potential side effects when given to an Alzheimer’s patient.

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Aducanumab has just been approved by the Food and Drug Administration to slow the progress of Alzheimer’s disease. It is likely that many people who are candidates for the drug will no longer be competent to make their own health care decisions and will be relying heavily on others to make the decision with them or for them.  As a layperson, how would I evaluate the risks and benefits of this drug, were I acting as a health care proxy for someone with Alzheimer’s disease? 

A number of years ago, when my mother was in the middle of her 10-year decline into dementia, her physician wanted to give her Aricept (donepezil) and was very unhappy when I turned it down. At first it had seemed to me that anything was worth a try. There was evidence that some people experienced small, temporary benefits in cognitive function and activities of daily living.  On the other hand, my mother had problems swallowing pills and hated to take any medication.  Her caregiver was reluctant to coax my mother to take yet one more pill. Side effects included nausea, vomiting, weight loss, dizziness, diarrhea, drowsiness, weakness, trouble sleeping, shakiness, and muscle cramps. My mother already weighed about 90 pounds soaking wet, so even minor weight loss was a worry. Dizziness meant higher risk of falls. Intestinal distress, for someone who was already upset about the loss of dignity associated with bathroom issues, seemed like a really bad idea. All of this might have made sense for someone willing to take on the risks and downsides for the sake of the possible benefit—but my mother could hardly be called willing, as she no longer understood cause and effect. 

My mother is long gone, but I thought of my decision on Aricept when the FDA announced its approval of aducanumab. How would I decide whether to have this drug prescribed for a family member?  I am pretty sure I would say no. And that is assuming that there was a choice: at over $50,000 a year, it is not clear who will be able to pay for it. I would ask myself: does the drug work? What are the risks? What are the side effects?  And how would taking the drug affect the overall quality of life of someone with Alzheimer’s? 

First, it is not at all clear that the drug works, in terms of affecting cognition and slowing decline. As Jason Karlawish explains in an incisive piece in STAT, crucial scientific steps were missed, and the current data are inconclusive and contradictory. 

Side effects include possible brain swelling and bleeds (which appear to be severe in about 6% of patients), headache, falls, diarrhea, and what Biogen describes as “confusion/delirium/altered mental status/disorientation.”  Wait a minute!  I thought the reason to take this drug was that one already had altered mental status and confusion.

Before someone is even considered eligible for aducanumab, they must take a PET scan to ascertain that they have elevated levels of amyloid and then an MRI to make sure they don’t already have brain swelling. MRIs must be repeated regularly while people are on the drug. I know perfectly competent adults who are freaked out by MRI’s.  How do you explain this to someone with dementia?  Or do you sedate them, thus adding to the risk? Furthermore, the drug itself is not a pill, but a monthly infusion. 

Put that all together, and it just doesn’t add up. How would my mother’s life change for the better? There is little evidence of the drug’s efficacy. Meanwhile, her peaceful life in her rural home with her dedicated caregiver would now be punctuated by trips to the hospital for MRI’s, and monthly struggles to start infusions in her 90-year-old body, with its tiny veins and paper-thin skin. Aducanumab is apparently best suited to people in the early stages of Alzheimer’s, but even in the earliest stage my mother refused to accept that she had a problem. I cannot imagine successfully explaining that we were taking these measures in the faint hope of combatting a problem she insisted she didn’t have. And in the absence of an explanation she could understand, surely the frequent hospital trips would feel to her like unpleasant, even scary, invasions.

Like most people with a family member with dementia, I would have crawled on my knees over broken glass to get access to something that helped, even if that help was merely to slow down the inevitable.  Sadly, aducanumab is not that help. I just hope that all the family decision-makers out there can resist the pressures of guilt, hope, desperation, and the need to do something, that they will take a deep breath and decide what is best for their loved one. (6/11/2021)

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My question is when presented with the hope that treatment could forestall the advances of Alzheimer’s, would most loved ones ask these questions or rely on the optimism of a select group of scientists versus a consensus group?

And a comment by Bonnie Steinbock, one of my professors in my Masters in Bioethics program. “Excellent piece…. I can’t decide if the FDA is just weak (scared of the Alzheimer’s Association and other lobbies) or corrupt (in the pockets of Big Pharma) or both.”

Other than the side effects mentioned by Dr Davis, there is an affordability factor that will limit access. Ethically, we are not supposed to bring cost into the discussion, but we all deal with the cost of premiums, co-pays in or out of network, insurance or no insurance when making decisions about treatments.

Aduhelm would be covered under Medicare Part B since it is an infusion and considered a procedure. In 2017, nearly 2 million Medicare beneficiaries used one or more of the currently available Alzheimer’s treatments covered under Part D, the part of Medicare that covers typical medications taken by mouth or injection.

Medicare Part B is funded by premiums and general taxes so will not face insolvency, unlike Medicare Part A which is projected to be insolvent by 2024. Beneficiaries will, however, face higher premiums. According to KFF.org,

“if just one-quarter of these [2 million beneficiaries] are prescribed Aduhelm, or 500,000 beneficiaries, and Medicare pays 103% of $56,000 in the near term, total spending for Aduhelm in one year alone would be nearly $29 billion paid by Medicare and the patients who use this drug – an amount that far exceeds Medicare Part B or Part D, based on 2019 spending. To put this $29 billion amount in context, total Medicare spending for all Part B drugs was $37 billion in 2019.”

Biogen estimates that 80% of Aduhelm patients will use Medicare Part B which could double what Medicare spends on all Part B drugs.

The projected cost for Aduhelm does not include an individual’s out-of-pocket co-pay or co-insurance expenses associated with related requirements for continued treatment. Some estimates range between $7550 to $11300 annually. Those costs include PET scans (typically not covered), co-pay and co-insurance fees for frequent MRIs, and multiple follow up specialty visits, whether in or out of network, along with various referrals that are required. And this assumes there are no complications which could significantly increase out of pocket expenses for the individual.

So you say… “many of these patients are covered by Medicaid so there is no cost to them.” True, but the escalating costs of Medicaid, borne by the states and its taxpayers, impact every part of our lives. Increasing Medicaid costs strip funds for education, public safety, and infrastructure.

Drug companies are required to conduct post-approval studies to verify the anticipated clinical benefit. These studies are known as Phase 4 confirmatory trials. If the confirmatory trial does not verify the drug’s anticipated clinical benefit, FDA has regulatory procedures in place that could lead to removing the drug from the market.

Tristan Massie, a biostatistics reviewer at the FDA, “does not agree that the totality of the data provides sufficient evidence to support the (effectiveness) of aducanumab in Alzheimer’s disease and does not recommend approval,” according to one document.

In response, Biogen noted in a written statement it has nine years to complete a study confirming the benefit of the Alzheimer’s treatment.

Nine Years! The demands on our healthcare system are stretching limited resources to a breaking point. I argue that Biogen should bear the cost until Phase 4 confirmatory trials validate a clinical benefit. If Biogen is so certain this is the long-awaited treatment for Alzheimer’s, then step up! Until then, don’t put this on the backs of patients or taxpayers.

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