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The Food and Drug Administration is now under the microscope in a congressional probe of its controversial approval of Alzheimer’s disease drug Aduhelm (aducanumab).

In a letter to the FDA sent last week, chairs of the U.S. House Committee on Energy and Commerce and the Oversight and Reform committee asked for information that would help explain how the drug met accelerated approval criteria when so many experts — including internal advisers — have determined that there was insufficient safety and efficacy data to do so.

Committee members expressed concern about “apparent anomalies” in the agency’s speedy review of the drug. They also flagged reports of “unusual coordination between FDA and Biogen throughout the drug’s approval process.” 

To facilitate Adulhem’s approval, FDA and Biogen relied on a post hoc analysis of cancelled clinical trials. This analysis showed that the drug successfully reduces amyloid beta plaque in the brain. But there is no established link between reduced amyloid brain plaques and slowed cognitive decline in Alzheimer’s patients, committee members wrote in a Sept. 2 news release.

“Prior to Aduhelm’s approval, FDA itself did not consider the reduction of amyloid beta plaque to be a surrogate endpoint likely to result in clinical benefit, raising additional questions about the drug’s approval process,” stated Frank Pallone, Jr. (D-NJ) and Carolyn B. Maloney (D-NY). 

Congressional investigators began their probe in July, asking drugmaker Biogen to turn over documents related to the approval and the company’s marketing process. 

A separate review of FDA’s interactions and accelerated approval process is also underway by the Department of Health and Human Services Office of the Inspector General, congressional lawmakers reported. The OIG probe follows a request by FDA Acting Commissioner Janet Woodcock, M.D., who said she feared that reports of unofficial contact between Biogen and FDA reviewers outside of the formal drug trial review process would undermine the public’s confidence in the agency.

Lack of clinician support

The drug does not have a wide base of support among clinicians. Since Aduhelm’s approval in June, a major long-term care physicians group has said it does not endorse it. At least two major hospital systems — Cleveland Clinic and Mount Sinai — and the Veterans Health Administration have said they will not administer it. Aduhelm’s hefty $56,000-a-year price tag has also sparked questions about affordability and its potential impact on Medicare and treatment equity.

Clinical trials have not shown evidence of safety or efficacy in the long-term care setting, said AMDA – The Society for Post-Acute and Long-Term Care Medicine, in a statement following the drug’s approval. What’s more, the high cost and need for sophisticated neuroimaging can be expected to widen inequitable care gaps, it said.

AMDA has called for more support of public health campaigns to reduce modifiable risk factors for Alzheimer’s such as vascular disease, as well as legislation that supports effective caregiving and care models for dementia.

In related news:
Biogen offers Alzheimer’s drug at no cost  The maker of Alzheimer’s drug Aduhelm (aducanumab) is offering no-cost treatment to some patients. Medicare has been slow to review claims for the drug, and Biogen’s move is meant to expedite real-world treatment using the drug, according to Reuters. “Mainly because of the uncertainty around insurance coverage … most doctors and systems are in a holding pattern,” Anton Porsteinsson, M.D., director of the University of Rochester Alzheimer’s Disease Care, Research and Education Program, told the news outlet. His health system is only using Aduhelm on patients enrolled in clinical trials. But at least some clinical practices have taken up Biogen’s offer.