The U.S. FDA has approved Aduhelm (aducanumab) developed by Biogen, Cambridge, Massachusetts, for the treatment of Alzheimer’s. Aduhelm was approved using the ‘accelerated approval pathway’.
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.
Aduhelm is the first new treatment approved for Alzheimer’s since 2003 and is the first approved therapy that targets the fundamental pathophysiology of the disease – the amyloid plaques in the brain.
However, the rapid approval has caused consternation in some sectors of the industry. According to STAT News three members of the FDA’s advisory committee resigned in protest over the decision. Writing in STAT News, Sam Gandy, a professor of neurology and psychiatry at the Icahn School of Medicine at Mount Sinai, argues that reducing amyloid plaques in the brain shows no clinical benefit. He also notes that there were no direct comparison trial data upon which to base a comparison of Aduhelm to donanemab or to lecanemab, two other experimental Alzheimer’s drugs that work in similar ways as Aduhelm.
Commenting on the FDA’s approval of the drug, Patrizia Cavazzoni, M.D., director of the FDA’s Center for Drug Evaluation and Research, explained: “Currently available therapies [for Alzheimer’s] only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer’s. As we have learned from the fight against cancer, the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation.”
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 timedependent reduction of amyloid beta plaque, while patients in the control arm of the studies had no reduction of amyloid beta plaque.
According to the FDA, 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.
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, diarrhoea, and confusion/delirium/altered mental status/disorientation.
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.