A congressional investigation has revealed that FDA's controversial approval of Biogen's Alzheimer's drug Aduhelm was "rife was irregularities" that overlooked internal concerns about the drug's safety and efficacy—leading one expert to call it "the worst decision the FDA has ever made."

Congressional report criticizes FDA, Biogen over Aduhelm approval process

In June 2021, FDA approved Aduhelm on a conditional basis—a move that many health experts pushed back against amid limited data on the drug's efficacy. In the months after, several health systems, including Cleveland Clinic and the Department of Veterans Affairs, declined to offer the treatment to their patients, and Medicare significantly limited its coverage of the drug.

Soon after the Aduhelm's approval, two congressional committees, the House Energy and Commerce Committee and the House Committee on Oversight and Reform, opened an investigation into FDA's approval process of the treatment.

The 18-month investigation included multiple briefings with FDA, as well as a review of over 500,000 documents from both FDA and Biogen. The committees also reviewed a prior internal investigation by FDA into Aduhelm's approval process.

In its investigation, the committees found that FDA's approval of Aduhelm was "rife with irregularities" and "raise serious concerns about [the agency's] lapses in protocol."

Between July 2019 and July 2020, FDA and Biogen created a "working group" to analyze Aduhelm's clinical trials, engaging in at least 115 meetings, calls, and email exchanges—interactions that the report called "atypical." The committees also found that at least 66 calls and email exchanges were not properly documented.

In addition, FDA partnered with Biogen on a joint briefing document that was presented at an advisory committee meeting. Such collaborations were typically rare, occurring only nine times before—typically for cancer drugs.

According to the report, the collaboration "was not an appropriate approach," largely due to internal conflicts over Aduhelm's safety and efficacy. In particular, FDA's statistical team argued there was insufficient evidence of Aduhelm's benefits for patients.

The report also highlighted concerns with Aduhelm's accelerated approval status, which it "abruptly" gained after "unfavorable feedback" from an advisory committee through the traditional approval process. Granting Aduhelm accelerated approval was also against FDA's guidance for Alzheimer's drugs, which stated the disease had not yet met "the standard for accelerated approval."

In addition, FDA initially recommended Aduhelm for all patients with Alzheimer's, despite the drug only being tested in patients with early-stage disease. In fact, Biogen's advisors warned against a broad label for the drug, saying that it could lead to safety risks and other issues. However, it was only after public pushback and confusion that Biogen asked for Aduhelm's label to be narrowed.

The committees also criticized Biogen for its decision to set Aduhelm's price "unjustifiably high." Initially, Aduhelm was priced at $56,000 a year before it was halved to $28,800.

Response

According to Sidney Wolfe, founder of the advocacy group Public Citizen's Health Research Group, approving Aduhelm was "the worst decision the FDA has ever made" in the last 50 years. "It was an unprecedented alliance between the company and the FDA," he added.

Going forward, the House committees said FDA "must take swift action to ensure that its processes for reviewing future Alzheimer's disease treatments do not lead to the same doubts about the integrity of [its] review."

The report included three recommendations that it believed FDA should immediately implement, including:

• Keeping proper documentation of the agency's interactions with drug companies
• Creating clear protocols for when the agency can create joint presentations with companies
• Updating its guidance for the development of new Alzheimer's drugs

The report also recommended drug companies clearly communicate any safety and efficacy concerns to FDA and to "consider the value assessment made by outside experts including patient access, when setting drug prices."

In a statement, FDA said it "fully cooperated with the committees' evaluation and we continue to review their findings and recommendations."

However, the agency noted that its own internal investigation found "no evidence" that its interactions with Biogen were "anything but appropriate" and defended its practice of working with companies.

"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," FDA said. "We will continue to do so, as it is in the best interest of patients. That said, the agency has already started implementing changes consistent with the committees' recommendations."

For its part, Biogen said the company "stands by the integrity of the actions we have taken" and that "Alzheimer's is a highly complex disease and we have learned from the development and launch of Aduhelm." (Cohrs et al., STAT+ [subscription required], 12/29; Belluck, New York Times, 12/29; Firth, MedPage Today, 12/30; Bettelheim, Axios, 12/29; Johnson, Washington Post, 12/29; Gardner, Politico, 12/29)