U.S. approval of the Alzheimer's drug Aduhelm is already mired in controversy. Now a new study finds that most Alzheimer's patients could not have taken part in clinical trials that led to the green light.
In June, the U.S. Food and Drug Administration gave accelerated approval to Aduhelm (aducanumab) for treating patients with mild cognitive impairment or mild dementia from Alzheimer's disease.
The decision quickly came under fire because of the Biogen drug's high price -- $56,000 a year -- and questions about possible collaboration between regulators and the drug's maker.
Now, this new study points to other limitations.
The phase 3 trials of the drug showed an increased risk of certain adverse vascular events. Although the trials excluded elderly patients, those with certain chronic diseases and those using blood thinners, the FDA approved use of the drug in these patient populations without noting any precautions.
"Our findings are concerning given the broad FDA labeling for aducanumab," said researcher Dr. Timothy Anderson, an assistant professor of medicine at Beth Israel Lahey Health in Boston.
"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," Anderson said in a health system news release.
For the study, the researchers looked at Medicare claims among 27 million patients with either cognitive (mental) impairment, Alzheimer's disease or Alzheimer's disease-related disorders.
They found that most of these patients had one or more conditions that would have banned them from the aducanumab clinical trials, including cardiovascular disease, stroke, use of blood thinners, or being over 85.
For example, data showed that about 9 out of 10 patients with Alzheimer's disease-related dementia or Alzheimer's disease itself had at least one factor that would have excluded them from the trials. Similarly, 85% of patients with cognitive impairment had at least one disqualifying condition.
And more than three-quarters of those with Alzheimer's disease-related dementia had several of these disqualifiers, the researchers noted.
"Clinical trials of aducanumab studied relatively healthy participants who do not reflect the majority of older adults with dementia in the U.S.," Anderson said. "As a result, Medicare should consider restricting coverage for aducanumab to patients who meet the trial eligibility criteria."
He said additional clinical trials of the high-risk groups excluded from the prior trials should be required and include rigorous study of adverse events.
The report was published Sept. 14 in the Journal of the American Medical Association.
In July, it was reported that two Congressional committees were looking into the process that led to the drug's approval and its steep cost. Although an FDA advisory committee concluded there wasn't enough evidence to support the effectiveness of Aduhelm, the FDA approved it. Three of the advisory committee members then resigned.
For more on Alzheimer's disease, see the Alzheimer's Association.
SOURCE: Beth Israel Lahey Health, news release, Sept. 14, 2021