ADUHELM FAQ – updated 7/26/21
NAME: ADUCANAMAB, a monoclonal antibody developed by Biogen.
Brand Name: ADUHELM
What is it? This is the first new drug approved for the treatment of Alzheimer’s disease in eighteen years. Although it was tested on people with MCI or early dementia stage of Alzheimer’s (stage 3 or stage 4 Alzheimer’s disease) with a confirmed amyloid pathology, the initial label allowed use in all people with Alzheimer’s disease. The label was later revised to limit use to those with MCI or early-stage dementia, i.e. those with mild impairment.
How does it work? Aduhelm is the first drug which is disease modifying- it reduces Amyloid plaque (a biomarker for Alzheimer’s disease) in the brain. The theory is that reducing amyloid in the brain will likely lead to improved memory and thinking.
NOTE- There is very little to no evidence that this theory works, and reduction in amyloid has not resulted in clinical improvement (improved memory and thinking) in many other studies over the past decade or more.
When was it approved? June 7, 2021
When will it be available? It is available now, but only on a very limited basis and with private payment.
How was it approved? Despite the recommendation (10-1) against approval, the FDA approved Aduhelm on June 7, 2021. It was approved under an accelerated approval process, allowed for serious and life-threatening diseases, where the endpoint (result) is the expectation of clinical improvement, based on changes in a biomarker even though there is some uncertainty regarding the benefits of the drug.
This provisional approval requires a phase 4 confirming study, which will gather data for up to nine years. If at the end of this trial, there is no evidence that the drug improves memory and thinking the FDA can remove Aducanamab from the market.
Note that three members of the FDA’s Advisory Committee resigned in protest over the approval of Aduhelm.
There are two Congressional committees investigating the approval process[EC1] . The Acting Commissioner of the FDA has initiated an internal investigation into the process.
What was the evidence that it worked? There were two phase 3 trials. One failed, and the other showed some positive results but only after an analysis of additional data showing that cognitive decline slowed by .5 of a point on a 3-point scale, for those subjects who took a higher dose of the drug vs placebo (sugar pill). The higher dose showed a 23% slower cognitive decline than those on placebo. There are no claims that the drug improves daily function, only that decline will diminish (but will continue.)
What are the side effects?
ARIA (Amyloid Related Imaging Abnormalities) or brain swelling which usually resolves over time. Requires an MRI to diagnose before the 7th and 12th infusion. Some people experience small areas of brain bleeding as well.
Most people with swelling and bleeding in the brain do not experience symptoms, but some people experience some symptoms, such as headache, nausea, dizziness, confusion and vision changes.
Falls, diarrhea, increased confused or altered mental state are other side effects of Aducanamab.
What is the cost? Biogen has set the cost at $56,000 a year. Insurance has not agreed to pay for the treatment yet. Although it is hoped that CMS and other insurers will pay for the drug.
On July 12, 2021 CMS (the Center for Medicare and Medicaid Services) opened its comment period on Aduhelm, and will remain open until April 2022. Other insurance providers generally follow the lead of CMS in determining eligibility for reimbursement.
Costly imaging, such as a PET Scan and multiple MRIs are required. A PET Scan may be required to be eligible to receive the drug (to determine if amyloid is in the brain). CMS does not pay for PET scans for amyloid.
How is it administered?
It is not a pill; it is an infusion treatment (a needle placed in the arm will deliver the medication) and will require monthly sessions of 45 minutes to an hour at a specialized medical facility.
How long do the benefits last? The clinical trials lasted 18 months, and that is the only data we have so far.
Is it used with dementias other than Alzheimer’s? It is only approved for the treatment of Alzheimer’s disease, due to the way it works to reduce amyloid plaque. In the trials it was tested on those with MCI or early-stage dementia, with a proven presence of amyloid in the brain established through imaging and or testing. These tests may include PET scans, MRI’s, lumbar punctures, (spinal taps) and they may not be paid for by insurance or Medicare.
Where do I go to get additional information?
CaringKind recommends that individuals with Alzheimer’s and their family caregivers speak with their treating physician or healthcare professional for further guidance. If you need assistance locating an Alzheimer’s diagnostic or research center, please call our Helpline at 646-744-2900.
For further information see these statements by our research partner CureAlzheimer’s Fund https://curealz.org/news-and-events/new-drug-for-alzheimers-disease-aduhelm/
and a statement from Biogen: https://investors.biogen.com/news-releases/news-release-details/fda-approves-updated-aduhelmtm-prescribing-information-emphasize
FDA statement on the Accelerated Approval Program
“The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint. A surrogate endpoint is 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. The use of a surrogate endpoint can considerably shorten the time required prior to receiving FDA approval.
Drug companies are still required to conduct studies to confirm the anticipated clinical benefit. These studies are known as phase 4 confirmatory trials. If the confirmatory trial shows that the drug actually provides a clinical benefit, then the FDA grants traditional approval for the drug. If the confirmatory trial does not show that the drug provides clinical benefit, FDA has regulatory procedures in place that could lead to removing the drug from the market.
REFERENCES:
New York Times, June 5, 2021, Alzheimer’s Drug Poses a Dilemma for the F.D.A.
New York Times, June 8, 2021, F.D.A. Approves Alzheimer’s Drug Despite Fierce Debate Over Whether It Works
Biogen, ADUCANAMAB Package Insert 6/21
F.D.A. Accelerated Approval Program 10/26/2020
Sam Gandy, MD, PHD, July 13, 2021, Private Correspondence and Talking Points for his Patients. This represents Dr. Gandy’s professional opinion and not that of Mount Sinai School of Medicine.