Much Ado About Aducanumab

On June 7 of this year, the U.S. Food and Drug Administration approved the first new drug therapy for Alzheimer’s disease in nearly 2 decades, delivering a boost of optimism and hope in the long and difficult fight against Alzheimer’s disease. Known by its brand name Aduhelm, aducanumab was developed by biotechnology innovator Biogen Inc. to target one of the known indicators of Alzheimer’s, the accumulation of damaging beta-amyloid proteins (often referred to as ‘plaques’) in the brain.  Specifically, aducanumab breaks down and clears beta-amyloid from the brain. The underlying hypothesis presupposes that once damaging plaques are cleared from an Alzheimer’s brain, cognition and memory should improve.

Up to now, the drug therapies available to Alzheimer’s patients have focussed on delivering a concentrated boost of chemicals associated with learning and memory, thereby countering the degenerative impact of the disease. These therapies, while often providing temporary improvement of cognitive symptoms, are necessarily short-lived, as the relentless progression of the disease ultimately overwhelms any ground that may be gained. Recent pharmaceutical research has set its sights on tackling the underlying causes of Alzheimer’s, in a bid to stop or slow the development of the disease. Aducanumab is the first of these therapies to be approved by the FDA. An application has been filed with Health Canada, thus initiating the Canadian review and approval processes for the drug. This is exciting stuff for the Alzheimer’s community.

But there is a catch. The FDA approval process was expedited, and the approval was granted without any real, consistent evidence that the drug actually improves memory. In fact, in 2 separate clinical trials, one showed improved cognition among only those study participants with mild Alzheimer’s disease (and little to no improvement in those with moderate to severe disease) while the other could find no positive impact whatsoever. The FDA’s approval is conditional upon Biogen conducting another clinical trial to prove the drug’s effectiveness. So depending upon those results, the drug may be pulled from shelves. As well, the therapy (which will require intravenous infusions of the drug at 4-week intervals) is extraordinarily expensive, with estimates ranging from US$30,000 to US$60,000 per year. And lastly, clinical trials have exposed some troubling side effects, with 40% of subjects developing some brain inflammation, and others reporting headache, diarrhea, confusion and delirium.

While controversy swirls in the research and medical communities about the expedited approval of aducanumab, the advent of these new therapies is something to be celebrated. They are the result of a new generation of understanding about the causes and ravages of dementia. Many scholars suspect that the ultimate cure for Alzheimer’s will require a multi-faceted approach, as the accumulation of beta-amyloid is only one characteristic of what is clearly a very complex disease. There are other proteins that play a role in degenerative diseases of the brain, as well as brain inflammation and vascular irregularities such as mini-strokes. It may be that a cocktail of drugs and other interventions will be the magic bullet that the Alzheimer’s community is searching for. But whether or not Aduhelm lives up to its promise, it represents a step closer to finding a cure for Alzheimer’s disease.

Amy Lewtas, Founder of RetroSparX