FDA Approves Controversial Alzheimer’s Drug Despite Potential Harm

SILVER SPRING, Md. — The Food and Drug Administration on Monday granted its approval to aducanumab, an Alzheimer’s treatment developed by Biogen for use in patients, despite mixed clinical trial results for the drug. 

Prescribed under the brand name “Aduhelm,” the treatment is given intravenously and is meant to remove protein deposits from the brains of patients in the early stages of Alzheimer’s. The proteins are known to cause loss of memory and physical control over one’s body functions.

The effects of the drug were studied in two clinical trials — only one of which deemed Aduhelm as an effective treatment. Prior to its approval, experts on the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee concluded that it was unreasonable to maintain the clinical benefit of one successful trial as the primary evidence supporting its approval.

“We are well-aware of the attention surrounding this approval,” Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, said in a written statement. “We understand that Aduhelm has garnered the attention of the press, the Alzheimer’s patient community, our elected officials, and other interested stakeholders. With a treatment for a serious, life-threatening disease in the balance, it makes sense that so many people were following the outcome of this review.”

Cavazzoni continued, “Further, the data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit. There has been considerable public debate on whether Aduhelm should be approved. As is often the case when it comes to interpreting scientific data, the expert community has offered differing perspectives.”

In all of its evaluations, the FDA noted Aduhelm “consistently and very convincingly” led to a reduction in the level of amyloid plaques in patient’s brains on a “dose- and time-dependent” basis. Ultimately, the administration concluded the drug satisfied the standards of its “Accelerated Approval” pathway and was likely to produce clinical benefit.

Roughly 40% of trial participants experienced brain bleeding or swelling after receiving high doses of the drug, according to study results published by Biogen. Although most participants were either asymptomatic or experienced only headaches, dizziness or nausea, the effects of the drug caused 6% of high-dose recipients to withdraw from the study.

“We ultimately decided to use the Accelerated Approval pathway — a pathway intended to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit,” Cavazzoni continued in the FDA’s statement. “In determining that the application met the requirements for Accelerated Approval, the Agency concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy.”

The drug will now undergo a post-market study to determine its widespread effectiveness as an Alzheimer’s treatment. If the “Phase 4 trial” fails to demonstrate its effectiveness or leads to adverse health effects in patients, the FDA could subsequently rescind its approval — although it is not required by law.

Aduhelm is the first new Alzheimer’s treatment approved by the FDA since 2003. Roughly six million Americans and 30 million people worldwide have Alzheimer’s, according to analysis by the Alzheimer’s Association. Further, the number of new cases of Alzheimer’s and other dementias is expected to double annually by 2050.

“The consequences of FDA approval are as disturbing as they are vast,” Jason Karlawish, professor of Medicine and Medical Ethics and Senior Fellow of the Center for Bioethics at the University of Pennsylvania, wrote in an op-ed for Stat News. “Around two million Americans could be prescribed aducanumab, at an estimated cost that ranges from $20,000 to $50,000 per person per year. Biogen claims the benefits of slowing declines in cognition and day-to-day function are worth this price. I think the company is wrong, and I agree with the analyses by the Institute for Clinical and Economic Review; the data to make this case are murky and, even if they were clear, the drug’s benefits are ambiguous at best and not worth this cost. Putting it on the market will stress Medicare’s resources.”