aducanumab-controversy

Aducanumab – The Controversy

During an educational session I did for the employees of Bank of America, I was asked about a drug the FDA just approved – aducanumab. This drug is designed to slow the progression of cognitive decline in those experiencing MCI (Mild Cognitive Impairment) and early stage dementia. Although there are multiple classes of drug that aim to reduce some of the symptoms of dementia, aducanumab is the first to actually slow the decline of dementia. The only problem is that was only proven to slow dementia’s progression in about 20% of those taking it in clinical trials prior to its FDA approval.

Actually that’s not the only problem. The cost of aducanumab, marketed by manufacturer Biogen as Aduhelm, is unconscionably expensive at a projected $56,000 per person. Per year.

Controversy examined

At that particular educational session, which was offered through the Alzheimer’s Association, I outlined the controversies around aducanumab. I spoke in the voice of the Alzheimer’s Association, which was the obvious voice to use considering it was the association that brought me to the dance, so to speak. As a Community Educator for the association, I am (gratefully) invited to address many corporate audiences, which often are the best attended events. So why wouldn’t I deliver messages consistent with the association’s views and research? But the association has also gently requested that we do so when we are representing it. And they have made it easy to deliver their message, by providing POV documents to support our effort. The most recent I received was from Harry Johns himself. Johns is the Alzheimer’s Association CEO.

POV: Alzheimer’s Association

Here is the association’s stance on the drug and the controversies surrounding it (in my words). I will add my own two cents after that.

Two points of controversy center on the testing phase. The first considers the length of time of the approval process and the second focuses on efficacy.

First, critics point out that the clinical trials yielded conflicting and/or inconclusive results. These folks believe that more trials should have been conducted, with more consistent results, prior to earning FDA approval. The Alzheimer’s Association wants to have confidence in the approval process and supports inquiries that aim to understand that “treatment approval processes work as they should.”

Second, many believe that a 20% chance of actually slowing the devastation Alzheimer’s and dementia wreak on the brain is not a strong enough chance. The Alzheimer’s Association strongly advocated for the drug’s approval, emphasizing that the possibility of lengthening the amount of “precious time” a person has to spend with loved ones is one that has never before been possible. Having an option for treatment, and access to it, has long been in the association’s sites.

The third controversy is the cost. At $56,000, the cost is unacceptable in the eyes of the Alzheimer’s Association. Johns assured us that the association is engaging with the manufacturer, to make Aduhelm more affordable. It is also engaging with Medicare, Medicaid and private payer systems to expedite coverage and access.

I have no argument with the Alzheimer’s Association’s views on aducanumab. It’s been 2003 since a new drug for Alzheimer’s was introduced. Aduhelm will be the first to actually address amyloid beta plaques (long believed to be the cause of Alzheimer’s). This drug is desperately needed and any treatment option has been a long time coming.

POV: My few cents

The FDA says aducanumab qualified for its Accelerated Approval[1] pathway because it treats a “serious or life-threatening illness that may provide meaningful therapeutic benefit over existing treatments when the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.” The FDA defines a surrogate endpoint as “a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit.”[2] By using a surrogate endpoint, the FDA process can be greatly condensed.  

It’s important to know that the current approval is conditional. Biogen will have to conduct a third clinical trial to prove a clinical benefit. If the third trial does not yield a positive outcome, FDA can revoke the approval.

So far, aducanumab qualifies for accelerated approval based on transitive, A = C evidence rather than tangible evidence. That might be acceptable in a course on Logic, but 20% efficacy based on transitive evidence doesn’t translate to exceptionally strong odds, medically speaking. Thus, will it be prescribed?

Medicare will approve treatments for illness if the therapy is reasonable, necessary, and effective (based on an evidence-based process).[3] Under the accelerated approval of Aduhelm, it could be argued that the evidence-based criteria has yet to be met. One must wonder, will it be covered by Medicare, Medicaid, and private payers?

Even if prescribed, if it’s not covered, will it be administered? Practically no one can afford $56,000 per year. That’s more than a new car. (The average cost of a new car is more than $40,000[4] – a controversy all its own – but let’s not go there.)

There’s a final point, but not related to the approval process for aducanumab. Aduhelm will be for those with MCI and early stage Alzheimer’s. But most people are diagnosed with Alzheimer’s in the early stages of the disease, NOT in Mild Cognitive Impairment. Theoretically the optimum window for taking Aduhelm is half-closed, so to speak.

If one’s progression could be slowed earlier and perhaps more by starting treatment in MCI and continuing through early stage Alzheimer’s, it would buy the family their maximum length of “precious time” in Harry Johns’ words. Therefore it’s even more important to be attentive to cognitive health and monitor it steadily and seek medical advice if the slightest signs of changes that affect daily life are noted. Because you would need a diagnoses to have access to aducanumab, controversy or not.

P.S.

PS. I need to do more research on this: The FDA has approved Aduhelm for the treatment of Alzheimer’s. But MCI is not Alzheimer’s. The drug is designed to benefit those with MCI and early stage Alzheimer’s. Will those with MCI be shut out of any benefits that Aduhelm might deliver because their diagnosis does not meet the FDA standard? Will diagnoses of Alzheimer’s be falsely elevated by doctors’ attempts to give their patients with MCI access? To be continued…


[1] https://www.fda.gov/drugs/information-health-care-professionals-drugs/accelerated-approval-program

[2] https://www.fda.gov/drugs/information-health-care-professionals-drugs/accelerated-approval-program

[3] https://www.cms.gov/Medicare/Coverage/DeterminationProcess

[4] https://www.cnet.com/roadshow/news/average-new-car-price-records/