The Food and Drug Administration (FDA) has recently granted accelerated approval to aducanumab (marketed as Aduhelm) for treatment of people with the earliest symptomatic stages of Alzheimer’s disease. This medication is the first potentially disease-modifying therapy approved for the treatment of Alzheimer’s disease in the United States.

Additional information about aducanumab and its approval

What is aducanumab?

Aducanumab is a monoclonal antibody (a protein that helps your immune system target other proteins), and it is designed to help your body remove something called amyloid beta from the brain. Amyloid beta is an important protein involved in the progression of Alzheimer’s disease. Aducanumab is given intravenously (infused through a vein) monthly. Aducanumab does not cure Alzheimer’s disease, but one (of two) large clinical studies suggests that aducanumab may slow the progression of the earliest symptoms of Alzheimer’s disease.

What does “accelerated approval” mean?

Aducanumab holds an “accelerated approval” from the FDA, which differs from the FDA’s traditional full approval. The FDA sometimes grants this special accelerated approval to enable earlier access to medications in serious diseases with limited alternative treatment options. Accelerated approval is sometimes granted to drugs that clearly improve laboratory or imaging measures of a disease, even if that drug’s effects on disease symptoms are not yet firmly established. Brain imaging studies with aducanumab confirm that it is able to remove amyloid beta plaques from the brain. Similar to other accelerated approvals, aducanumab will only maintain approval if its possible effects on early Alzheimer’s symptoms can be confirmed in a special follow-up clinical trial (called a “post-marketing study” or a “phase four clinical trial”).

Who might receive aducanumab?

Aducanumab should only be considered for use in people who have a firmly established diagnosis of Alzheimer’s disease in its very mildest symptomatic stages. This may include people with symptoms consistent with mild cognitive impairment or the very earliest stages of dementia.

The diagnosis of Alzheimer’s disease is currently best confirmed by detecting brain accumulation of Alzheimer’s disease proteins with either a lumbar puncture or an amyloid beta positron emission tomography (PET) scan of the brain (though newer blood tests for Alzheimer’s disease may be similarly helpful for diagnosis when they become clinically available). Before considering treatment for Alzheimer’s disease, a person must first seek care from a specialist with the expertise necessary to complete an appropriate diagnostic assessment. The UCSF Memory and Aging Center Clinic is one of many centers with expertise in diagnosing Alzheimer’s disease.

What are some potential risks of aducanumab?

About 4 in 10 patients who receive aducanumab develop a kind of brain inflammation called amyloid-related imaging abnormalities (ARIA), which involves brain bleeding, brain swelling, or a combination of the two. Close to 1 in 10 people who receive aducanumab will likely need to discontinue their treatment due to concerns related to ARIA. People who carry a specific gene version called ApoE4 are particularly susceptible to developing ARIA. Only 3 in 10 people who develop ARIA experience symptoms. About 1 in 10 patients with ARIA may appear to have severe changes on brain imaging scans, though severe symptoms and complications occur in less than 1 in 100 patients with ARIA. The potential risks and benefits of aducanumab must be thoroughly considered in each person individually. Some patients with Alzheimer’s disease may not be appropriate for treatment with aducanumab, due to their doctor’s concerns about their individual balance of possible risks and benefits from treatment. Additionally, before and after aducanumab is started, patients must receive special monitoring (including brain magnetic resonance imaging [MRI] scans) to screen for ARIA.

Next steps at UCSF

Providers at UCSF have not started prescribing aducanumab. UCSF is currently determining how aducanumab might be considered for use in appropriate patients already receiving care at the UCSF Memory and Aging Center. Additionally, we do not yet know if health insurance companies will cover treatments with aducanumab. The Centers for Medicare and Medicaid Services (CMS) announced on July 12, 2021, that they have begun their initial review to consider the possibility of coverage for aducanumab treatments. CMS will release its decision between January and April of 2022.

If you or your loved one is worried about new and progressive concerns with memory, language or behavior, the first best step is to consult with a doctor and specifically consider a referral to a neurologist. If you are specifically interested in receiving diagnostic assessment and care at UCSF, please contact the UCSF Memory and Aging Center Clinic for guidance on seeking a referral.