The US Food and Drug Administration (FDA) has approved Biogen’s regulatory application for the use of aducanumab in the treatment of Alzheimer’s disease, which removes amyloid from brains. Aducanumab is the first new Alzheimer’s drug in nearly 20 years, and there is reportedly mixed evidence over its efficacy. However, according to expert commentary, the “desperate need for treatment” makes it likely that governments across the world will strive to make the drug available after this US approval.
Alzheimer’s disease is characterised by a decade-long build-up of a protein in the 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 is a human monoclonal antibody discovered with Neurimmune’s Reverse Translational Medicine technology and licensed to Biogen who co-developed it with Eisai. Research at Neurimmune, in collaboration with the University of Zurich, led to the identification of protective anti-amyloid antibodies in healthy elderly people and patients with slowly progressing dementia. These antibodies bound brain amyloid in patient tissues. Study of the antibodies resulted in the discovery of aducanumab. Following intravenous administration, aducanumab crosses the blood-brain-barrier, binds to brain amyloid, and removes it with the help of the immune system.
“The data of three separate clinical studies unequivocally show that aducanumab’s biological activity removed amyloid from brains of patients with Alzheimer’s disease. Based on our understanding of the disease, substantial amyloid removal is required to slow disease progression” said Roger Nitsch, CEO of Neurimmune. “Our outstanding 14-year collaboration with Biogen succeeded in bringing this new treatment option to patients and their physicians.”
In clinical trials, Biogen has demonstrated that aducanumab reduced brain amyloid in a dose- and time-dependent manner. Amyloid was reduced by 59 to 71% at 18 months of treatment. Accelerated approval has been granted based on aducanumab’s reduction of amyloid, an effect that is reasonably likely to predict clinical benefit, in this case to slow disease progression.
John Growdon, Professor of Neurology at the Harvard Medical School and Senior Clinical Advisor of Neurimmune, said: “Today’s approval of aducanumab for Alzheimer’s disease is a historic breakthrough for patients, families and society.”
Despite the previously mentioned concerns, University of Manchester biochemist Professor Andrew Doig argues that the drug is a positive step and will pave the way for even greater advances. He said: “Aducanumab works by breaking down the amyloid-b protein clumps that are present in the brains of Alzheimer’s victims, using antibodies. However, we don’t yet know whether removing amyloid-b can reverse the cognitive effects of Alzheimer’s, such as loss of short-term memory. In addition, the treatment is likely to be very expensive and may have unwanted side effects.”
He continued: “Our company, PharmaKure, has a unique approach to identify off-label compounds that also break down amyloid-b clumps, but with few side effects and a cost-effective price. We are excited about Aducanumab as it paves the way for more effective drugs for Alzheimer’s that tackle the root cause of the disease. We hope that effective treatments for this debilitating disease will be available for all, sooner, rather than later.”