Congress Asks FDA for More Information on Aduhelm Approval

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Federal lawmakers are asking the U.S. Food and Drug Administration (FDA) to provide additional data and documents related to the agency’s controversial decision to grant accelerated approval to Biogen‘s Aduhelm (aducanumab) as a treatment for Alzheimer’s disease.

U.S. Rep. Frank Pallone, Jr., chair of the House Committee on Energy and Commerce, and U.S. Rep. Carolyn B. Maloney, chair of the Committee on Oversight and Reform, wrote in a letter to acting FDA commissioner Janet Woodcock, MD, that they are “concerned by apparent anomalies in FDA’s processes surrounding its review of Aduhelm.”

“We are also concerned by reports of unusual coordination between FDA and Biogen throughout the drug’s approval process,” they added.

In the 13-page letter to Woodcock, the members of Congress requested that the FDA answer 15 separate and multipart questions about the agency’s approval of Aduhelm. The deadline for providing the information to lawmakers is Sept. 16.

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Aduhelm is an antibody-based therapy designed to clear amyloid-beta plaques from the brain. These plaques, formed of abnormally folded proteins, are a hallmark of Alzheimer’s disease, the progressive neurodegenerative disorder that is the most common cause of dementia.

Early clinical trial data indicated that Aduhelm could effectively clear these plaques, leading Biogen to launch two Phase 3 clinical trials to test whether the therapy might affect cognition. Biogen halted the trials in early 2019, after an interim analysis suggested Aduhelm was unlikely to be beneficial.

Data later available revealed that Aduhelm had significantly slowed the decline in cognition and function — namely in terms of memory, orientation, and language, as well as in activities of daily living — in one Phase 3 trial, but that no such benefit was seen in the other trial. Despite these inconsistent results, Biogen decided to seek FDA approval of Aduhelm in late 2019.

An FDA advisory committee voted strongly against approving the medication in late 2020, saying that the available data were not enough to ensure the medicine’s efficacy.

Nonetheless, earlier this year, the FDA granted Aduhelm accelerated approval. This specific type of approval is given based on preclinical measurements — in this case, the reduction in amyloid-beta plaques. A condition of accelerated approval is that the therapy’s maker conduct additional testing to demonstrate efficacy.

The FDA amended its approval a few weeks later, specifying in the therapy’s label that it should only be used to treat patients with early disease, the population on which the medication was tested during clinical trials.

The decision to approve Aduhelm based on its effect on amyloid has been controversial: the congressional chairs even noted that the link between these abnormal protein plaques and Alzheimer’s cognitive decline “is not well-established and has even been questioned.”

Additionally, at the advisory committee meeting in late 2020, the FDA stated that it was “not using the amyloid as a surrogate for efficacy.” Accelerated approval also was not discussed as a possibility at the advisory committee meeting.

Aduhelm’s approval sparked three of the committee members to resign in protest, with one calling it “probably the worst drug approval decision in recent U.S. history.”

A congressional investigation into Aduhelm’s approval was launched less than a month after the approval was announced. The medication’s high price — about $56,000 per year — also has drawn criticism.

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Since the approval of Aduhelm, it has come to light “that experts in FDA’s own Office of Biostatistics raised concerns about the ‘inconsistency’ of the drug’s supporting clinical data,” Pallone and Maloney wrote.

Furthermore, allegations have emerged that representatives of Biogen and the FDA may have conducted meetings related to the investigational therapy that were not recorded in the proper channels. FDA officials have acknowledged that not all communication with Biogen officials was correctly documented.

In light of these concerns, the congressional chairs are requesting a slate of new data and documents from the FDA. For instance, they are asking to see the specific data that led the agency to conclude in its initial approval that a reduction in amyloid-beta is reasonably likely to predict clinical benefit.

They also are requesting detailed documentation about how the decision was made, such as why accelerated approval was not discussed as a possibility with the advisory committee, and how internal disagreements among agency staff were resolved. Details about the FDA’s discussions with Biogen, and plans for further studies of Aduhelm, also are requested.

“We applaud efforts to advance brain health equity and make strides toward eradicating Alzheimer’s and we share in the hope for new advancements to treat this debilitating and costly disease. However, it is critical that these treatments be safe, effective, and accessible,” the chairs wrote.

“To help ensure that the American people continue to have the utmost confidence in FDA and the safety and efficacy of approved drugs, and to help inform future legislation, we need more information about FDA’s process for reviewing and approving Aduhelm,” they concluded.