By Genni Burkhart
According to a recent annual report by the Alzheimer's Association, more than 6 million people in the United States are living with Alzheimer’s Disease (AD). Perhaps more staggering, by 2050 this number is projected to more than double to 13 million, with the national costs for treatment expected to reach 1.1 trillion dollars over the same timeframe. The disease trajectory in this 2021 report is dire, highlighting how ill-equipped the current armamentarium is at confronting this all-out public health crisis.
Researchers have yet to discover the root cause of AD, but there’s overwhelming agreement that brain plaque is a contributor. Researchers have linked family history, education, and chronic conditions such as heart disease and diabetes to AD and various forms of dementia.
The FDA Draws Criticism
Until recently, treatments for AD were primarily symptomatic, meaning they improve symptoms without actually curing or altering the underlying cause of the disease. That all changed on June 7, 2021, when The Food and Drug Administration (FDA) contentiously approved the drug Aduhelm (aducanumab) from Biogen under the accelerated approval pathway.
In their approval, U.S. regulators stated Aduhelm was “reasonably likely” to benefit AD patients as the only therapy approved to treat the underlying disease pathology, rather than just symptomatic treatment. Experts have overwhelmingly disagreed with this approval, intensely rebuking it and calling it the worst mistake in FDA history. This decision is considered to be the most controversial decision by the FDA in years–so much so that:
- Two congressional committees are now investigating the cost and approval of Biogen’s drug Aduhelm.
- The FDA is performing an “undisclosed” internal inquiry.
- Expert panel members have resigned.
- FDA acting commissioner Dr. Janet Woodcock called for an inspector general to investigate the agency’s approval process after mounting pressure.
- The non-profit public advocacy group, Public Citizen has called for Dr. Janet Woodcock to be removed.
According to an article by the New York Times, the 15 officials who make up the council overseeing complex issues at the FDA agreed another clinical trial would be necessary before giving their approval of Aduhelm. The NYT obtained minutes of the meeting where one council member said, “Approval could result in millions of patients taking aducanumab without any indication of actually receiving any benefit, or worse, cause harm.”
As researchers and medical experts contend with this situation, the question remains– does Aduhelm offer hope or hurdle in treating Alzheimer’s Disease?
Aduhelm (aducanumab) Trial and Tribulations
Biogen conducted randomized trials of high and low-dose versions of the drug on patients diagnosed with early onset Alzheimer’s Disease. These trials were split into two phases with three placebos.
Two years ago Biogen halted their Aduhelm (aducanumab) trials due to inconclusive evidence of benefit. Brain swelling or brain bleeding was also reported during these trials and is noted on the Biogen website. This lack of evidence caused scientists to question if the theory behind this drug, the amyloid hypothesis, was actually wrong, given the amount of time that had passed without a conclusive finding.
Then after further review, Biogen changed course by stating greater analysis of the trial data showed their treatment was successful at slowing down the decline in AD patients. Thinking skills in patients taking aducanumab saw a 22% slower decline than patients taking a placebo. This difference equated to just a 0.39 improvement on an 18-point score of cognitive and functional ability. It’s not clear how this translates into practical benefits to the patient such as improved independence or memory recall.
Upon this discovery, trials were restarted, and the 3,500 study participants once again began receiving monthly infusions.
The Controversial Approval Process of Aduhelm
The FDA acknowledged that while Aduhelm did not adequately demonstrate a conclusive ability to slow AD progression, it did show the ability to remove plaque and was, therefore, “Reasonably likely to predict a clinical benefit to patients.” The FDA then granted Aduhelm an accelerated approval based on this theory — a regulatory route that officials had previously told the advisory committee last November wasn’t under-considered.
Aaron Kesselheim, director of Brigham and Women’s Hospital’s Program on Regulation, Therapeutics, and Law, was the third advisory committee member to resign in protest, and described the approval of Aduhelm as, “Probably the worst drug approval decision in recent U.S. history.”
Further, the FDA was found to have unusually close contact with Biogen during the approval process. It was revealed that in 2019 Biogen and the FDA had multiple meetings to “jointly assess” the research data and together map out a route of success that included making concerted presentations to a committee of independent experts. This led many to question not only the current acting commissioner but the entire approval process at the FDA.
Biogen has set a price of $56,000 for the drug which was shown to be far over the reasonable production and research cost of this drug. This has caught the attention of Medicare, which is conducting a rare investigation into the approval of this drug, as it carries the potential to add hundreds of billions of dollars to Medicare spending each year.
Both Sides of the Argument
There are many advocacy groups, patients, and their families making a strong argument for the approval of any new therapy, even those with small benefits, as deserving of FDA approval. In a Washington Post op-ed, three directors at the Center for Drug Evaluation and Research (CDER) at the FDA support the approval, writing, “While aducanumab’s trials suggested — but did not confirm — clinical benefit, they did convincingly and consistently show that the drug reduces amyloid plaque in the brain, a defining pathological characteristic of Alzheimer’s disease.”
However, countless experts warn against giving drug manufacturers easier and faster FDA approval under lower thresholds. They argue it will lead to a dangerous precedent– opening the door for treatments with questionable benefits, decreased public trust, and reduced research and funding for legitimate therapies.
The approval of Aduhelm is one of the most controversial decisions by the FDA in years. Some doctors are prescribing this medication with caution, while others are awaiting further proof of its efficacy, as investigations into FDA approval are guaranteed. In listening to the voices of the people diagnosed with Alzheimer’s Disease, it’s clear this disease doesn’t simply rob people of their memories, but of their entire identities. The strongest argument for Aduhelm just might be the hope it offers those facing this inescapable reality.
Author: With over 11 years as a published journalist, editor, and writer Genni Burkhart’s career has spanned across politics, healthcare, law, business finance, and news. She resides on the western shores of the Puget Sound where she works as the Editor in Chief at DOCS Education out of Seattle, WA.