Individuals receiving aducanumab showed significant dose- and time-dependent reduction of amyloid beta plaque, whereas patients in the control arm had no reduction, according to the FDA.
Officials with the FDA have approved aducanumab (Aduhelm) for the treatment of Alzheimer disease, representing the first major treatment approval since 2003, according to a press release.1
Alzheimer disease is an irreversible, progressive brain disorder that gradually destroys memory and thinking skills, as well as the ability to carry out basic tasks. Although specific causes of the disease are unknown, it is characterized by changes in the brain, such as amyloid plaques and neurofibrillary tangles, which result in the loss of neurons and their connections.1
“Our current treatments for things like Alzheimer’s disease and some of these degenerative dementias are symptomatic medications…they all try to help the symptoms,” said Douglas Scharre, MD, a neurologist and director of the division of Cognitive Neurology at Ohio State Wexner Medical Center, in an interview released by the medical center. “But none of them that are available right now get to what a lot of people think are the core issues to modify the disease.”2
Aducanumab was approved under the accelerated approval pathway and is a first-of-its-kind treatment for Alzheimer disease. Investigators evaluated its efficacy in 3 separate studies including 3282 patients. Individuals receiving the treatment had significant dose- and time-dependent reduction of amyloid beta plaque, whereas patients in the control arm had no reduction, according to the press release.1
The reduction of amyloid beta plaque in the brain was a surrogate endpoint supporting the accelerated approval of aducanumab. According to the press release, the presence of amyloid beta plaque in the brain is a hallmark of Alzheimer disease.1 The plaque was quantified using positron emission tomography imaging to estimate the brain levels of amyloid beta plaque in a composite of brain regions, which are expected to be widely affected by the pathology of Alzheimer disease.1
Prescribing information for aducanumab includes a warning for amyloid-related imaging abnormalities, which typically present as swelling in areas of the brain. This swelling usually resolves over time and does not cause symptoms, although some patients may experience headache, confusion, dizziness, vision changes, or nausea.1
The drug also includes a risk of hypersensitivity reactions, including angioedema and urticaria. The most common adverse effects seen in clinical trials were amyloid-related imaging abnormalities, headache, fall, diarrhea, and confusion or altered mental status.1
“Alzheimer’s disease is a devastating illness that can have a profound impact on the lives of people diagnosed with the disease as well as their loved ones,” said Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, in the press release. “Currently available therapies only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer’s.”1
As part of the accelerated approval provisions, the FDA is requiring Biogen to conduct a new randomized, controlled clinical trial to prove the drug’s clinical benefit. If the trial findings do not prove this benefit, the FDA may initiate proceedings to withdraw the approval.1
"This approval is a victory for people living with Alzheimer's and their families," said Harry Johns, president and CEO of the Alzheimer's Association, in a statement. "This is the first FDA-approved drug that delays decline due to Alzheimer's disease. This means individuals may have more time to actively participate in daily life, have sustained independence and hold on to memories longer. We can experience longer—the relationships we hold most dear, our families and friends."