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The Problem with Aducanumab: Approved For Alzheimer's

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Aducanumab has given a lot of families, patients, doctors, and nurses hope. However, the FDA approval of this drug is very controversial. I present both sides, giving voice to those that support it and those who do not.

Specializes in Geriatrics, Home Care, Senior Care. Has 15 years experience.

Is there any hope for Alzheimer's patients using Aducanumab?

The Problem with Aducanumab: Approved For Alzheimer's

Nurses who work with Alzheimer patients and their families do not have to be told about the anguish these families go through as they watch a loved one leave them as they are still physically present.  And in the early stages of the disease, the patient also watches what is happening. They have needed hope for a long time.  So now there is a new drug, Aducanumab. There is a catch, however, a controversy.  I will attempt to present both sides of this controversy, giving voice to those who support the drug and those who don’t.

The approval and use of Aducanumab feels like a storm; it has happened so fast. It was approved just this June by the Food and Drug Administration. To those of us paying attention, it feels like it has already been a few years. Three members of the Food and Drug Advisory committee that reviewed the findings of the tests for Aducanumab resigned over its approval. Yet the Food and Drug Administration backs its decision, and patient advocacy groups are thrilled at this seeming breakthrough. Many families and loved ones of patients, and patients themselves, see it as making headway. It is the first novel therapy to be approved for Alzheimer’s since 2003.

Aducanumab is an enormous aberration for the FDA. Throughout history, medicine men and later legitimate pharmaceutical companies could sell their wares without proving that they actually work. That ended with the debacle of thalidomide in the 1950s and 1960s. Around the world, many women gave birth to babies with severe birth defects because of this drug that was given for nausea. Dr. Frances Kelsey worked at the American Food and Drug Administration at the time. He pretty much single-handedly made sure the drug did not enter the U.S. Marketplace. Soon after that, the U.S. Congress passed a law (1962) that required pharmaceutical companies to prove extensive drug testing before any medicine can be put to market.

Aducanumab (to be marketed as Aduhelm) has been approved against the recommendation of the FDA’s own committee. It has been reported several places, perhaps first, and most notably, by Laurie McGinley in the Washington Post, that the Peripheral and Central Nervous System Drugs Advisory Committee was asked to vote on the drug’s effectiveness. There were a few questions about the evidence. There was not one “yes” vote. Ten members voted no and one uncertain. Yet Aduhelm was still approved under the umbrella of what is known as an accelerated approval pathway. It was approved and announced on June 7, 2021.1

The Food and Drug Administration’s Center for Drug Evaluation and Research director is Patricia Cavazzoni, M.D. She was quoted by the publication Salud America! as saying on June 7, “Alzheimer’s disease is a devastating illness that can have a profound impact on the lives of people diagnosed with the disease as well as their loved ones. Currently available therapies only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer’s. As we have learned from the fight against cancer, the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation.”2

At least one other doctor echoes her position. Dr. Rany Aburashed is Chief of Neurology at Memorial Healthcare in Michigan. Memorial Healthcare is a hospital with an institute for neuroscience. Jacqueline Howard reported that he was quoted from an email: “…. What is really exciting is that Aducanumab is the first new FDA-approved Alzheimer’s treatment in 20 years, and we’re optimistic this will spark a wave of new research and innovation in this space. Patients are excited for that, too, and if aducanumab is the first step toward that bright future, patients are eager to be part of it.”3

Biogen and its Japanese partner Eisai are the pharmaceutical companies that developed Aducanumab. They claim that the drug slows the decline of mental acuity and cognitive health in Alzheimer’s patients. Again, Jacqueline Howard of CNN reports that Biogen’s documents presented to the committee at the FDA stated that the patients that were given high-dose aducanumab showed 22% less clinical decline in their cognitive health than those who were given a placebo. This was after 18 months of medication.

Aducanumab, or Aduhelm, targets amyloid beta plaques. Jacqueline Howard of CNN quotes Dr. Aburashed as writing: “This is the first antibody directed treatment for Alzheimer’s disease that targets the main possible cause of the disease, which many feel is related to the deposition and accumulation of a protein called amyloid beta. The antibody binds to aggregates of the amyloid protein and appears to preferentially target the amyloid plaques in the brain as opposed to those in the blood vessels.”4

Still, the tests were not enough to satisfy the committee at the FDA. And their reaction to Aduhelm’s approval is radical. The first to resign from the FDA for this was Dr. Joel Perlmutter. He is a neurologist at Washington University School of Medicine in St. Louis. He was quoted as saying, “Approval of a drug that is not effective has serious potential to impair future research into the treatments that may be effective.” He was followed in his exit by Dr. Aaron S. Kesselheim, professor of medicine at Harvard Medical School. Dr. David Knopman was the third to leave the FDA. He is a clinical neurologist at The Mayo Clinic. According to several publications, including The Washington Post, he wrote in an email to FDA officials “Biomarker justification for approval in the absence of consistent clinical benefit after 18 months of treatment is indefensible.”5

The problem with Aducanumab, or Aduhelm as it will commonly be known, is that patients and families are so desperate for something, anything that just might work. There are two major issues with the drug. It has been known to cause the brain to swell and hemorrhage. The other drawback is that it costs $4,312 per infusion, making an annual cost of $56,000 for a high dose. It is infused intravenously over about an hour every four weeks. Nurses know the implication of that – it acts fast, and there is little time to turn back if there is an adverse reaction. Is there an antidote yet to Aduhelm?

Nevertheless, people are anxious to take the drug or see their loved ones take the drug. Kurt Rehwinkel is a spouse to a patient taking Aduhelm. He does not understand people who want Aduhelm kept off of the market. He said in an interview with NPR’s Jon Hamilton, “I wondered, do these people really have loved ones who have a stake in the game? Are they losing a little bit more of their loved one every day to the disease?”6

As nurses, one of our jobs in all of this will be, as always, to listen empathetically to these patients and their families, giving them as much time, space and reprieve as we can. As always, we have to leave our own opinions to the side while offering compassionate care.


References/Resources

1,5 Two Members of an FDA Advisory Committee Quit After Approval of Controversial Alzheimer’s Drug   

2 FDA’s Decision to Approve New Treatment for Alzheimer’s Disease

3,4 New Alzheimer’s Drug Aducanumab: Cost, Side Effects, Timeline and Other Questions Answered

6 For Those Facing Alzheimer’s, a Controversial Drug Offers Hope

FDA Grants Accelerated Approval for Alzheimer’s Drug

Aducanumab (Marketed as Aduhelm) Information

FDA’s Decision to Approve New Treatment for Alzheimer’s Disease

Three FDA Advisers Resign Over Agency’s approval of Alzheimer’s Drug

FDA Approves New Drug for Alzheimer’s, But Scientists Divided Over Decision

FDA Grants Accelerated Approval for Alzheimer’s Drug

Nadine Buchanan has 15 years experience as a LPN and specializes in Geriatrics, Home Care, Senior Care.

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6 Comment(s)

I guess my question to you is, how many patients have had brain bleeds and what is causing it?  I don’t know that swelling is a huge issue especially with Alzheimer’s patients as their brains have already atrophied from the natural aging process and the disease process of Alzheimer’s itself.  
 

And why did these people resign?  I guess I’m confused by this article.

It’s not uncommon for an elderly person to have a brain bleed.  Many of the elderly are on some type of blood thinner.  They fall, get massive brain bleeds.  They are also at a higher risk of a brain bleed if given TPA when having an ischemic stroke.

Maybe the solution is to do frequent neuro checks during each infusion like what is done with the administration of tpa.  The risk of hemorrhagic conversion with tpa is like 29% so I’d like some hard numbers on this medication.  

CalicoKitty, BSN, RN

Specializes in Med-Surg, Geriatrics, Wound Care. Has 9 years experience.

On 8/25/2021 at 9:42 AM, LovingLife123 said:

I guess my question to you is, how many patients have had brain bleeds and what is causing it?  I don’t know that swelling is a huge issue especially with Alzheimer’s patients as their brains have already atrophied from the natural aging process and the disease process of Alzheimer’s itself.  
 

And why did these people resign?  I guess I’m confused by this article.

I don't know why there would be hemorrhages, but I will assume it is because this medication passes the brain barrier and attacks structures (amyloids) in the brain, causes swelling (probably immune response) and results in bleeding.

The members of the advisory quit because they were completely ignored - 90% of them voted "no" and 1 of them was "unsure". None of them supported the approval of the medication. And despite the overwhelming no, the advisors were ignored and the medication was approved.

 

The drug label notes that in two studies, ARIA (amyloid related imaging abnormalities) was observed in 41% of patients treated with the approved dose of aducanumab compared to 10% of patients who did not receive the treatment.

Basically this treatment attacks the plaques. The theory is that destroying the plaques will slow the disease progression. The problem is that there is no evidence to support this theory, despite previous trials with other medications that would reduce the plaques. Of their 2 studies, one showed no benefit, and another showed a possible 22% reduction in cognitive decline after 18 months.

Aside from the $5k/dose for the medication, regular MRIs are also a part of the plan to monitor the 41% of patients that get the ARIA.

On 8/25/2021 at 9:42 AM, LovingLife123 said:

 The risk of hemorrhagic conversion with tpa is like 29% so I’d like some hard numbers on this medication.

 

Hemorrhagic conversion after alteplase is less than 6%, FYI.

Nadine Buchanan, LPN

Specializes in Geriatrics, Home Care, Senior Care. Has 15 years experience.

Thank you all for your thoughtful comments. I don't have any answers without doing more research for another article. I too will be watching for more answers. I merely wanted to bring up the controversy, and show both sides if I could. The reaction to those who left the FDA because they thought principals had been compromised is just rare.

JBMmom, MSN, NP

Specializes in Long term care; med-surg; critical care. Has 9 years experience.

Years ago when I worked in pharmaceutical research I was one of the genetic toxicologists assigned to the rare disease research team. We had a drug progress into clinical trials with patients for a disease that is known to be fatal to patients beginning in their 20s. I also had a cousin whose son was battling this same disease and had tried to enroll him in the clinical trial. She was aware that two families had children that received treatment and saw a significant improvement in their condition within weeks. Other families did not have such positive results, but for the families that did they had shared the news among family networks. Our company was flooded with requests for patients to receive this drug in clinical trials. Unfortunately, we were unable to achieve statistically significant results and the program was disbanded.

This was a crushing defeat for the families that had seen promise only to have it taken away. One of the challenges with pharmaceutical research is that just like disease progression is individual to the patient, so is the response to proposed treatments. What works for some may not work for others, but the FDA is bound by relatively strict parameters when approving drugs, and for good reason. If tylenol were being developed by a company today, chances are the FDA would not approve it, the safety profile might prevent it. However, politics and such play a role in how it is still currently available and relatively unregulated. 

Is this Alzheimer's drug going to be a life changing therapy for some patients? Maybe. And if it is then they will benefit from the FDAs decision. If some people suffer unwanted side effects, will their family still think the risk was worth the potential benefit? Hard to say. The whole system is very complicated and sometimes it feels like no one really wins in many instances. 

Nadine Buchanan, LPN

Specializes in Geriatrics, Home Care, Senior Care. Has 15 years experience.

Thank you for this. Very informative, interesting.