FDA Grants Accelerated Approval for Alzheimer’s drug Aduhelm

USFDA approved Aduhelm (aducanumab) for the treatment of Alzheimer disease. Alzheimer’s drug Aduhelm is research molecule of Neurimmune. Neurimmune licensed its antibody Aducanumab for the treatment and prevention of Alzheimer’s disease to Biogen in 2007, and collaborates with Biogen on its development.

Aducanumab is a human monoclonal antibody discovered with Neurimmune’s Reverse Translational Medicine technology and licensed to Biogen who co-developed it with Eisai. 

Key Points to note:

• Aduhelm was approved using the accelerated approval pathway, which can be used for a drug for a serious or life-threatening illness that provides a meaningful therapeutic advantage over existing treatments. Accelerated approval can be based on the drug’s effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients, with a required post-approval trial to verify that the drug provides the expected clinical benefit.
• Under the accelerated approval provisions, which provide patients suffering from the disease earlier access to the treatment, the FDA is requiring the company, Biogen, to conduct a new randomized, controlled clinical trial to verify the drug’s clinical benefit. If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug.
• At the same time, Aduhelm was granted Fast Track designation, which seeks to expedite the development and review of drugs that are intended to treat serious conditions where initial evidence showed the potential to address an unmet medical need.
• Aduhelm represents a first-of-its-kind treatment approved for Alzheimer’s disease. It is the first new treatment approved for Alzheimer’s since 2003 and is the first therapy that targets the fundamental pathophysiology of the disease.

Aducanumab mechanism of action

Alzheimer’s disease – the leading cause of dementia in elderly people – is characterized by a decade-long build-up of a protein in brain known as amyloid. It can damage the brain’s nerve cells resulting in progressing deficits in memory, learning, orientation in space and time, language, and thoughtful planning. Amyloid is readily detectable in affected brains and its removal is a therapeutic objective in Alzheimer’s disease.

Aducanumab removes amyloid from brains (Sevigny J. et al., 2016). It is a human monoclonal antibody discovered with Neurimmune’s Reverse Translational Medicine technology and licensed to Biogen who co-developed it with Eisai. Aducanumab is the first approved treatment to slow Alzheimer’s disease.

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Clinical basis of approval

Researchers evaluated Aduhelm’s efficacy in three separate studies representing a total of 3,482 patients. The studies consisted of double-blind, randomized, placebo-controlled dose-ranging studies in patients with Alzheimer’s disease. Patients receiving the treatment had significant dose-and time-dependent reduction of amyloid beta plaque, while patients in the control arm of the studies had no reduction of amyloid beta plaque.

These results support the accelerated approval of Aduhelm, which is based on the surrogate endpoint of reduction of amyloid beta plaque in the brain—a hallmark of Alzheimer’s disease. Amyloid beta plaque was quantified using positron emission tomography (PET) imaging to estimate the brain levels of amyloid beta plaque in a composite of brain regions expected to be widely affected by Alzheimer’s disease pathology compared to a brain region expected to be spared of such pathology.

Warning in Aduhelm label

The prescribing information for Aduhelm includes a warning for amyloid-related imaging abnormalities (ARIA), which most commonly presents as temporary swelling in areas of the brain that usually resolves over time and does not cause symptoms, though some people may have symptoms such as headache, confusion, dizziness, vision changes, or nausea. Another warning for Aduhelm is for a risk of hypersensitivity reactions, including angioedema and urticaria. The most common side effects of Aduhelm were ARIA, headache, fall, diarrhea, and confusion/delirium/altered mental status/disorientation.

About Alzheimer’s Disease

Alzheimer’s is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually, the ability to carry out simple tasks. While the specific causes of Alzheimer’s disease are not fully known, it is characterized by changes in the brain—including amyloid plaques and neurofibrillary, or tau, tangles—that result in loss of neurons and their connections. These changes affect a person’s ability to remember and think.