The Aducanumab Controversy

FDA accelerated-approved Aducanumab removes beta-amyloid proteins involved in Alzheimer's amidst controversy.

Photo: AP

Alzheimer's Disease

Affecting at least 50 million people worldwide, Alzheimer's is a progressive neurological disorder that results in brain atrophy and is also the most common cause of dementia.

Photo: Bagad M., Towards understanding Alzheimer's Disease: An Overview (2013)

Brain atrophy is a result of a disruption of communication between neurons, with the main characteristic being the abnormal build-up of beta-amyloid proteins collected between the neurons, resulting in amyloid plaques.

Pharmacology

Aducanumab is a monoclonal IgG1 antibody which binds to amyloid-β at amino acids 3-7, reducing the extracellular amyloid plaques as per the "amyloid cascade hypothesis".

An intravenous dose of 10 mg/kg has a Cmax of 182.7 µg/mL and a Tmax of 3 hours, as well as a terminal half-life of 24.8 days.

Clinical Trials and Controversy

Although given accelerated approval by the FDA on 7 June 2021 for patients with mild Alzheimer's, their initial clinical review had not reached any statistically valid conclusions and the data could not provide sufficient evidence of the efficacy.

Furthermore, there was a high percentage of trial subjects (35.2%) experiencing amyloid-related imaging abnormalities (ARIA-E) such as oedema compared to placebo subjects (2.7%), and a number of subjects (18-22.7%) experiencing ARIA-related microhemorrhages (ARIA-H), suggesting that there might be high risks of administering high doses at 10 mg/kg.

Although EMERGE trial data had shown a positive effect with trial subjects given Aducanumab compared to placebo, ENGAGE trial data only showed that Aducanumab presented clinical benefits at high doses and only specific to the areas of memory and reasoning skills.

However, a recent Yale study has shown a visible reduction of amyloid plaques during an autopsy of a patient who had previously been treated with Aducanumab over 32 months.

Thus, as per the conditions of the accelerated approval, continued approval will be based on further trials to determine clinical benefits over current therapies.

Who Can Take Aducanumab?

As recommended from clinical trials,

• People with mild Alzheimer's

• Evidence of amyloid plaque buildup in the brain

• Younger than 85 years of age

• No history of microbleeds or stroke due to bleeding

• Not on blood-thinning medications

Disclaimer: Do not self-medicate. Approach your healthcare provider for more information.