Congressional Report Finds FDA Ignored Agency Protocols in Approving Biogen’s Aduhelm Alzheimer’s Drug

Biogen and FDA held numerous improperly documented meetings designed to drag Aduhelm through the approval process despite a lack of evidence showing the drug worked, the report found

Concerns have been raised about whether federal drug regulators failed to follow their own standard protocols when approving the controversial Alzheimer’s disease drug Aduhelm, after a new Congressional report suggests that the FDA had an unusually close relationship with Biogen, the manufacturer.

Aduhelm became the first novel therapy approved for the treatment of Alzheimer’s since 2003, after it was granted approval through the FDA’s Accelerated Approval Program in June 2022. The drug is designed to reduce the presence of amyloid beta plaques in the brain, which are believed to be linked to the progression of the disease. However, the decision to approve the medication immediately raised questions, since it followed the unanimous recommendation against approval by a panel of independent advisors to the FDA, due to questions about Aduhelm’s effectiveness treating Alzheimer’s.

Following an 18 month investigation that looked into why the drug was approved, a joint report was released this week by the U.S. House of Representative’s Committee on Oversight and Reform, and Committee on Energy and Commerce, titled “The High Price of Aduhlem’s Approval” (PDF), highlighting the overly cozy releationship between the FDA and Biogen.

The agency’s approval led to several members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee resigning in protest, and several congressional committees are looking into the decision. The agency has since faced a number of serious questions, such as why the FDA approved the drug when its own experts said it should not, and whether there was an improper working relationship between the agency and the drug’s manufacturer, Biogen.

Lawmakers Question FDA, Biogen Relationship and Aduhelm Approval

House staffers reviewed more than 500,000 pages on documents and held multiple briefings with the FDA.

“The Committees’ review of these materials reveals that FDA’s review and approval of Aduhelm consisted of atypical procedures and deviated from the agency’s own guidance,” the report determines. “These materials also reveal that Biogen had aggressive launch plans for Aduhelm – including in its label and pricing – despite concerns about efficacy, safety, and affordability.”

The House report notes that the FDA’s accelerated approval of Aduhelm occurred despite the fact that Biogen had cancelled clinical trials for the Alzheimer’s drug in March 2019. Aduhelm is supposed to reduce amyloid beta plaque in the brain, but an independent report at the time found it was unlikely to be a benefit to Alzheimer’s patients and determined no further clinical trials should be conducted.

However, just three months after the clinical trials were cancelled, FDA staff members and Biogen formed a “working group” which engaged in at least 115 meetings, calls and email discussions over the next year. At least 40 of those meetings were focused on dragging Aduhelm through the approval process despite evidence the drug just did not work. The House investigators found some of the meetings were not properly documented according to FDA protocols, raising suspicions.

The report determined that the FDA’s interactions with Biogen were atypical, failing to follow the agency’s documentation protocol on many occasions, making it hard to determine what happened at those meetings. At least 40 working group meetings between FDA staff and Biogen, 66 phone calls and a substantial number of email exchanges were not properly documented, House staffers determined.

House investigators also found that the FDA and Biogen inappropriately collaborated to create a joint briefing document for the FDA Advisory Committee. Even that was not enough to prevent the FDA’s advisors from resoundingly rejecting Aduhelm, which did not stop the FDA from approving it.

“The Committees obtained evidence that FDA and Biogen staff worked closely for several months ahead of the November 6, 2020, PCNS Advisory Committee meeting to prepare the joint briefing document for the Committee’s review,” the investigators wrote. “Documents show that using a joint briefing document afforded Biogen advance insight into FDA’s responses and direct guidance from the agency in drafting the company’s own sections.”

Despite the failed clinical trials, and despite the rejection by the FDA’s own panel of advisors, the agency granted Aduhelm accelerated approval anyway, and then when the drug came out, investigators found that Biogen planned to set an unusually high price of $56,000 per year for treatment. Then the company planned to spend $3.3 billion to market the drug, which is three times how much it cost to develop.

“The findings in this report raise serious concerns about FDA’s lapses in protocol and Biogen’s disregard of efficacy and access in the approval process for Aduhelm,” the report concludes “The criticism surrounding Aduhelm’s approval pay have been avoided had FDA adhered to its own guidance and internal practices. FDA must take swift action to ensure that its process for reviewing future Alzheimer’s disease treatments do not lead to the same doubts about the integrity of FDA’s review.”