top of page

Aducanumab (ADUHELM) for Alzheimer's

Updated: Nov 20, 2021

Aducanumab (ADUHELM)

Phonetic pronunciation: a du CAHN ue mab / AD yew helm

Pronounce Aducanumab (Aduhelm) by Jason Cafer MD (phonetic pronunciation)
Medication Mascot aducanumab (Aduhelm)
Download P • 395KB

Aducanumab (Aduhelm) was approved in June 2021 as an immunotherapy for treatment of Alzheimer’s disease (AD). Aducanumab is a monoclonal IgG antibody that stimulates the immune system to attack amyloid β (beta) peptides, which are the main component of amyloid plaques found in the brain of individuals with AD. Aducanumab can cross the blood-brain barrier to help clear neurotoxic amyloid β to reduce its buildup. This is the first treatment directed at the underlying pathophysiology of AD instead of just addressing dementia symptoms. It is also the first monoclonal antibody approved for any psychiatric indication.

Aducanumab has been proven to reduce amyloid plaques but has not been proven to improve clinical outcomes in AD. The "amyloid hypothesis" that the plaques are responsible for AD is accepted by the majority of researchers and it is presumed that plaque reduction will to lead to a reduction in cognitive decline in AD. There was considerable debate on whether aducanumab should have been approved. The FDA accepted the medication through the Accelerated Approval pathway—which provides access to important therapies despite uncertainty regarding clinical benefit. The manufacturer is now required to conduct trials to verify the drug’s anticipated benefit. If aducanumab fails to improve cognitive functioning, the FDA can (but is not required to) rescind its approval. Some other drugs in clinical trials are more promising, but are years away from potentially entering the market.

The drug also reduces neurofibrillary tangles composed of tau protein.

Aducanumab is administered intravenously once monthly. Duration of the clinical trial was 1 year. The drug will cost $56,000 yearly not including cost of brain MRIs. Aducanumab is broadly approved “for the treatment of Alzheimer’s disease”. Clinical trials, however, only included individuals in early-stage Alzheimer’s whose brains contained high levels of amyloid via PET scanning. The label states there are no contraindications for the drug.

Aducanumab is associated with 35% risk of brain edema or microhemorrhage. One subject died. 24% of patients reported side effects (versus 5% on placebo), most commonly headache. 8% of patients experienced confusion / delirium / disorientation / altered mental status (versus 4% with placebo). 6% percent of recipients discontinued aducanumab due to side effects. Hypersensitivity reactions including angioedema and urticaria have occurred.

The dose must be titrated with full strength not reached until the 7th monthly infusion. Enhanced vigilance for symptoms of brain swelling or bleeding is necessary during the first 8 months of treatment, particularly during titration. Brain MRI is required prior to the 7th and 12th infusions to check for Amyloid-Related Imaging Abnormalities due to Hemosiderin deposition (ARIA-H) which can be indicative of microhemorrhage or superficial siderosis (iron deposition). If an MRI shows severe ARIA-H, treatment may be continued with caution only after a clinical evaluation and a follow-up MRI demonstrates radiographic stabilization (i.e., no increase in size or number of ARIA-H deposits). ARIA-E means brain Edema.

Interactions for aducanumab (Aduhelm) from Cafer's Psychopharmacology

Steady-state concentrations of aducanumab were reached by 16 weeks of repeated dosing. Monoclonal antibodies are not affected by pharmacokinetic interactions. They are degraded into small peptides and amino acids in the same manner as endogenous IgG antibodies.

The full generic name of the medication is aducanumab-avwa. The four-letter suffix has no pronunciation or meaning. Such suffixes are added to biologic drugs to distinguish reference products from their biosimilars. The suffix "-mab" is used for monoclonal antibodies. More specifically “-umab” signifies that the product is a humanized antibody, i.e., an antibody made in the laboratory by combining a human antibody with a small part of a animal antibody, the Chinese hamster in this case. The hamster part of the antibody binds to the target antigen and the human part makes it less likely to be destroyed by the immune system.

More on amyloid β: The normal function of amyloid β is not well understood. Animals with absence of amyloid β do not demonstrate any obvious problems. Amyloid β plaques are neurotoxic. The glymphatic system clears amyloid β from the brain, a process that is increased during sleep. Autosomal-dominant mutations in amyloid precursor protein (APP) cause hereditary early-onset Alzheimer's disease. Amyloid β plaque formation is prominent in adults with Down Syndrome, contributing to early-onset dementia.

Dosing: Aducanumab is administered by intravenous infusion over one hour every four weeks (at least 21 days apart). The titration schedule is 1 mg/kg for infusions #1 and #2, then 3 mg/kg for infusions #3 and #4, then 6 mg/kg for infusions #5 and #6, then 10 mg/kg for infusion #7 and beyond. Obtain a recent (within one year) brain MRI prior to initiating treatment and prior to the 7th and 12th infusions.

270 monographs like this can be found in Cafer’s Psychopharmacology: Memorize to Visualize 270 Medication Mascots available at

787 views0 comments


bottom of page