June 21, 2021
Regarding the provision of aducanumab to patients of the UNC Division of Cognitive and Behavioral Neurology:
Recognizing the controversy surrounding this drug’s recent approval by the FDA, we are currently developing a set of guidelines in conjunction with several other leading North Carolina academic partners, with the intention of providing this drug in the safest manner possible. Our intention is to provide treatment to those who meet both of the basic criteria identified by Biogen’s prior studies: (1) amyloid-positive by either lumbar puncture or PET scan, and (2) still at the Mild Cognitive Impairment stage (FAST stage 3) of disease. In addition, we intend to enroll all patients who begin treatment at our institution in a patient registry that will allow us to systematically evaluate response to therapy and monitor drug safety.
At the moment, this drug is not yet available to the UNC community as Biogen has not yet shipped doses of drug, nor has UNC completed the process of adding it to our formulary. Just as importantly, the Centers for Medicare and Medicaid Services (CMS) have not yet determined whether, and under what circumstances, they will be willing to pay for the drug. Given that the full annual cost is in excess of $50,000, we will not begin offering the drug until we can assure fair and equitable access to as broad a segment of our clinical population as is feasible.
We will post updates to this aducanumab policy as they are developed. In the meantime, we ask for your patience.
Andrea Bozoki, MD, FAAN
Professor and Division Chief, Cognitive and Behavioral Neurology
Heidi L. Roth, MD, FAAN
Associate Professor, Cognitive and Behavioral Neurology
Director, UNC Aging Brain Clinic
What do I need to know about the new drug approved by the FDA for Alzheimer’s disease?
The drug that was recently approved by the FDA, called aducanumab, also known by the brand name of Aduhelm, is an intravenous (IV) infusion that may be given once per month, in monthly installments, to patients with Alzheimer’s disease.
Does aducanumab work?
As noted in the FDA labelling for this medication, there is no clear evidence that this medication improves symptoms in Alzheimer’s disease. There were two large clinical trials, each of which had two groups that received aducanumab (low dose and a high dose group in each study). Each of the four groups that received the medication had about 500 patients. Another group did not receive any medication (placebo). Both trials were stopped early, because no benefit was seen. However, with a re-evaluation, they found that one of four of the groups that received the medication had a small symptom benefit.
How big was the benefit in one of the four groups? On a common scale used to measure memory and thinking, the Mini-Mental Status Exam ( MMSE), the change was 0.6 / 30 points. One point is often thought to be necessary to show a clinically meaningful benefit for the MMSE. On the 85-point Alzheimer’s Disease Assessment Scale – Cognitive (ADAS-COG-13) score, one of the four groups made a 1.4 point change, and 3 points is usually thought to be meaningful on that scale. Some people think the change was due to chance, and more studies would be needed to determine if this was the case. It is important to realize that the benefit was very small, and might be due to chance.
None of the studies has been made publicly available or has been published in peer-reviewed format.
The studies were done with people who have early memory problems and who were more likely to benefit from the medication. Eighty percent of the people in the studies had mild cognitive impairment, and the other 20% had early Alzheimer’s disease. There have been no studies in people with moderate or later stages of Alzheimer’s disease.
But I thought aducanumab clears amyloid in the brain which causes Alzheimer’s disease?
This is true; aducanumab does clear the amyloid protein in the brain, however, the medicine does not clearly change symptoms. This can seem confusing at first. If amyloid causes Alzheimer’s disease, why is it that when it is removed, symptoms do not improve? One theory is that when people start to have early Alzheimer’s disease, they have had amyloid in their brains for a long time; and the amyloid has already triggered other processes which are actually causing the continuing damage. If the amyloid has already done its job triggering the other processes, taking it away does not necessarily stop the other processes. So at this stage, the secondary processes need to be targeted as well. Scientists have focused on accumulations of the tau protein and inflammatory factors that cause nerves to deteriorate as being responsible for the progression and continuing changes of abilities in patients. It is possible that aducanumab might have effects on the tau protein, but this has not yet been proven.
What do the experts think about aducanumab?
Because of the controversy about whether there is any benefit for the symptoms in patients, the scientific advisory board to the FDA voted unanimously that the medicine should not be approved (with one abstaining vote).
At this time, aducanumab is projected to cost approximately $56, 000 a year, and it is not clear yet how much of this would be covered by insurance. Even for people with insurance, this medication could cost patients up to $10,000 per year (due to the 20% co-pay). Currently, it is not known what Medicare, Medicaid or private insurers will decide in terms of paying for the medication and which types of patients would qualify.
What are the risks?
This medication can cause a form of brain swelling called ARIA – E (Amyloid Related Imaging Abnormalities – Edema) in 20-40% of people enrolled in the trial. Typically, the symptoms are mild and reversible, but symptoms did result in about 6% of people in the high dose group leaving the study. One percent of the people with ARIA-E have severe symptoms (confusion, disorientation, gait problems, ataxia, visual disturbance, headache, nausea, falls, and blurred vision). In addition, there can be increases in small brain hemorrhages in 20% of patients. Typically, these complications happen early in the first six months, and resolve, but brain MRI monitoring must be done to evaluate for these side effects.
Another unknown risk for patients is that the studies only included people who were younger than 85 years old (while one-third of Alzheimer’s patients are older than 85). The studies also did not include people who are taking blood thinners. It would be important to know that the risks might be higher for a patient taking the medication who did not fit the criteria from the study.
Is this medication available now?
It is not yet available, but will likely be available soon. We are working with our partners at Duke, Wake Forest, and around North Carolina, to establish consensus guidelines for how this medication should be used responsibly and in which types of patients. Please see the current plans we are developing at UNC in the statement at the top of the page.
At this time, we expect that when this medication is offered, it will be offered to the patient population that was formerly studied in the trials. We also expect to have close monitoring for side effects by entering all patients into a registry to follow any progress or side effects. All patients who might be interested are likely to need a lumbar puncture prior to starting the protocol. We will have further details soon, but please see our section below on the current plans.
Recognizing our desire for medications that make a real difference
Most of us know people with Alzheimer’s disease. Maybe some of us have family members with this disease right now, or we might be concerned about close friends or loved ones with memory problems. We want you to know that we are all eager to have medications that make a difference for people’s lives in a disease that can be devastating and associated with such great personal loss for individuals and families. We encourage patients and their families to stay informed about all options to participate in research as well as obtain treatment that may offer benefits. We are excited to offer information and opportunities to participate in research and be enrolled in any trials with medications that may be beneficial.