Reactions to Aduhelm Report Blast FDA Closeness to Industry

Except for a defensive FDA statement (below), other reactions to a 12/30 report by two House committees on FDA’s 2021 controversial review and approval of Biogen’s Alzheimer’s drug Aduhelm are sharply critical of the approval and the agency’s decision to work so closely with the company to guide the drug’s review and approval. The report found FDA’s interactions with Biogen were atypical and that the agency had deviated from its own guidance on documenting meetings with industry.

FDA reviewers and Biogen staff held at least 115 meetings, calls and email exchanges over a 12-month period, and this number is likely greater because the agency lacked a “clear record” of informal meetings and other interactions between its staff and Biogen, the Oversight and Reform and Energy and Commerce Committees’ report found. It said many of the interactions were not memorialized as required by internal FDA procedures. It also found that FDA and Biogen “inappropriately collaborated on a joint briefing document” for an advisory committee review, and the document failed to adequately represent differing views within the agency.

The report noted that an FDA internal review of the briefing document collaboration found that CDER’s Office of Neuroscience had failed to obtain Office of New Drugs consensus on the agency’s position prior to working with Biogen on the document. The internal review concluded that “the use of the joint briefing document was not an appropriate approach in this instance” given the substantial disagreement between FDA offices. The internal review was sparked by a complaint from advocacy group Public Citizen that warned the close collaboration “dangerously compromised the integrity of FDA’s review.”

Additionally, the report recommended FDA take the following three actions to help restore trust in the agency’s processes and assurances of drug safety and efficacy:

• Ensure that all substantive FDA interactions with drug sponsors are properly memorialized;
• Establish a protocol for developing joint FDA-drug sponsor briefing documents for advisory committees; and
• Update its guidance on developing and reviewing new alzheimer’s drugs to provide the agency’s current view on how such drugs should be evaluated.

Former FDA reviewer and whistleblower (see earlier story) Ronald Kavanagh said he shared his analysis of Aduhelm’s publicly available review documents and found many troubling areas in FDA processes and procedures. In a 12/30 Twitter post, he said FDA was clearly biased in its approach to finding a way to approve Aduhelm when traditional approval did not seem to be a viable path. Kavanagh also complained that FDA wrongly allowed studies to be used as the basis for the accelerated approval that were not adequate and well controlled.

Many reactions to the report’s findings also took issue with Biogen setting an “an unjustifiably high price” for Aduhelm considering its adverse impact on patients and Medicare. The report cited internal company documents showing that the company initially set Aduhelm’s price at $56,000 per year despite a lack of demonstrated clinical benefit in a broad patient population. Presentations to Biogen’s board of directors stated that the company’s “ambition is to make history” and “establish Aduhelm as one of the top pharmaceutical launches of all time.” Documents also showed that Biogen projected the drug could represent about 36% of Medicare’s Part B budget, and it knew that some Medicare patients could face out-of-pocket costs for Aduhelm of up to 20% of their income.

Reacting to the report on Twitter, University of California San Francisco professor of medicine Vinay Prasad called the Aduhelm approval “probably one of the biggest scandals of all time for FDA… The FDA was helping a company approve a trash drug that doesn’t work just to bleed people with Alzheimer’s of their [money]. The saddest, cruelest thing possible.” An online essay by Prasad that was published shortly after Aduhelm’s approval (see earlier story) called FDA’s regulatory system “grievously and horribly broken,” saying there is no signal that it is getting better any time soon.

Aduhelm’s 2021 approval was met with much public concern and outrage, with many pointing to the unusual turn to accelerated approval following FDA’s 11/2020 Peripheral and Central Nervous System Drugs Advisory Committee meeting that voted down Biogen’s study data being considered for traditional approval (see earlier story). Interestingly, panel members were not asked for their input on whether accelerated approval was a viable option. Shortly after the drug’s approval and in protest of FDA’s irregularities, three of the panel members resigned (see story)

Advisory committee members at the meeting were persuaded by FDA’s statistical reviewer, Tristan Massie, wrote in a briefing paper that the one positive trial of aducanumab could not overcome the negative one (see earlier story). “There is no compelling evidence of treatment effect or disease slowing and … another study is needed to confirm or deny the positive study and the negative study,” she wrote. FDA Office of Neuroscience director Billy Dunn told the panel that issues with the negative trial don’t “meaningfully detract from the persuasiveness” of the positive trial.

The advocacy group Right Care Alliance applauded the House committees’ report detailing the “many irregularities” in FDA’s Aduhelm approval. The group said the report appears to “vindicate many of the criticisms that the Right Care Alliance and other organizations put forward after Aduhelm’s approval… People living with dementia deserve genuinely effective, safe, and affordable treatment options. We hope that someday such treatments will exist — but Aduhelm wasn’t it.”

In a statement provided to FDA Webview, FDA said: “When appropriate, FDA will continue to use the accelerated approval pathway, an authority granted to us by law that allows us to provide earlier access to treatments for serious or life-threatening illness, which includes neurodegenerative diseases.” It noted that an internal agency review of how CDER staff interacted with Biogen found that Center’s interactions were appropriate. “It is the agency’s job to frequently interact with companies in order to ensure that we have adequate information to inform our regulatory decision-making,” it said. Additionally, the agency said it has already started implementing the report’s recommended changes, such as examining the use of a joint briefing document and plans to update its guidance on new Alzheimer’s drugs.