In a controversial decision in June 2021, the U.S. Food and Drug Administration (FDA) approved a new Alzheimer’s medication in nearly two decades.
Now, researchers are saying that the patients involved in the study do not represent the majority of people with Alzheimer’s disease in the United States.
The Exclusion Criteria
In a research letter published in JAMA, Timothy S. Anderson, M.D., from Beth Israel Deaconess Medical Center in Boston, and colleagues evaluated whether patients in aducanumab trials indeed represent the majority of patients with dementia in the United States.
It found that the two phase 3 clinical trials in which the recent aducanumab approval was based used exclusion criteria. Particularly, the trials excluded participants based on:
- Advanced age (85 and older)
- Cardiovascular disease
- Chronic kidney disease
- Previous stroke
- Use of anti-blood-clotting medications
Still, Aduhelm (aducanumab) was approved without precautions for drug use in these particular patient populations. In other words, aducanumab may be used in patients whose conditions were not studied in the trials. This puts them at a higher risk of adverse events.
Furthermore, the above criteria would exclude the vast majority of Medicare beneficiaries with the following conditions:
- Alzheimer’s disease (AD)
- Mild cognitive impairment (MCI)
- Alzheimer’s disease-related disorders
“Our findings are concerning given the broad FDA labeling for aducanumab,” said author Timothy S. Anderson, MD, MAS, a clinician-researcher and assistant professor in the General Medicine Division at BIDMC.
“The public conversation on aducanumab has focused on limited benefit and high costs, it is equally important to consider that the majority of patients with Alzheimer’s disease are likely to face higher risks of adverse events than the patients studied in the trials.”
What the Research Found
Anderson and colleagues analyzed data from 27 million Medicare beneficiaries. They found that this number of patients met at least one of the aducanumab trial exclusion criteria:
- 92% of patients with Alzheimer’s disease-related dementia
- 91% of patients with Alzheimer’s disease
- 85% of patients with cognitive impairment
Furthermore, the team found that 77% of patients with Alzheimer’s disease-related dementia met more than one exclusion criteria, as with the majority of patients with other diagnoses.
Looking at the bigger picture, what does this really mean?
Let’s take it from the author himself:
“Clinical trials of aducanumab studied relatively healthy participants who do not reflect the majority of older adults with dementia in the US,” Anderson said.
“As a result, Medicare should consider restricting coverage for aducanumab to patients who meet the trial eligibility criteria, and additional clinical trials of the high-risk groups excluded from the prior trials should be required, including rigorous study of adverse events, prior to broadening coverage.”
Congressional Committees Demand FDA Documents on Aduhelm Approval
Earlier this month, house committees investigated the controversial approval of the new Alzheimer’s drug manufactured by Biogen.
Two congressional committees demanded detailed information and records from the FDA through a letter addressed to the agency’s acting commissioner, Dr. Janet Woodcock.
The 13-page letter made it clear that the committee chairs are concerned about the unusual steps that the FDA took in reviewing and approving the drug.
The letter was signed by Representative Carolyn Maloney, chair of the House Committee on Oversight and Reform, and Representative Frank Pallone, chair of the House Energy and Commerce Committee.
Specifically, the letter asks for information about each step of how the FDA handled Aduhelm, the brand name for aducanumab.
Aside from objections from the agency’s own advisors and officials, former Biogen senior medical director, Dr. Vissia Viglietta, also opposed the drug approval. The congressional letter also cited Viglietta’s objection, as she helped design the late-stage clinical trials of aducanumab.
She told The New York Times in July that the approval “defeats everything I believe in scientifically, and it lowers the rigor of regulatory bodies.”
The FDA responded to the letter through a statement. The agency said it would cooperate with Congress in light of the request for records and extensive information.
“The F.D.A. recognizes the need for new therapies and used a science-based approach that incorporated consideration of patient perspectives in its evaluation of the benefits and risks of this therapy,” the statement said.
