Investigation Into Alzheimer’s Drug Approval Process Requested By Multiple Entities, Including FDA

There are mounting calls for an investigation into the FDA’s controversial decision to approve a new Alzheimer’s drug, including a request by the head of the agency, after regulators were sharply criticized and several independent advisors resigned in protest.

On July 9, FDA Acting Commissioner Janet Woodcock sent a letter to the inspector general of the FDA, calling for an investigation into the approval of Biogen’s Aduhelm, and into interactions between Biogen and FDA staff. She said such an investigation was warranted given the high amount of criticism the FDA has received over the drug’s approval and accusations of an overly close relationship with the manufacturer.

The FDA granted accelerated approval of Aduhelm in early June, as the first Alzheimer’s disease therapy drug. However, the decision came after an FDA advisory panel nearly unanimously recommended against approval.

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.

Aduhelm is the first novel therapy approved for the treatment of Alzheimer’s since 2003, after being granted approval through the FDA’s Accelerated Approval Program. 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, in a November 2020 meeting of the Peripheral and Central Nervous System Drugs Advisory Committee, eight of the 11 members voted that one of the major clinical trials supporting approval of the drug did not provide strong evidence of Aduhelm’s effectiveness. Only one member of the committee voted “Yes,” and two others were uncertain.

The committee voted similarly on another study’s findings, which looked at the drug’s effectiveness, with seven members voting the evidence was not convincing, four voting they were uncertain, and none of the members voting they were convinced the study showed Aduhelm actually works.

A third vote on the overall evidence resulted in a 10-0 vote against whether there was primary evidence of Aduhelm’s effectiveness, with one member voting they were uncertain.

The decision sparked widespread controversy and criticism, which only increased after an investigative report by Stat (subscription required), published on June 29, detailed what appeared to be an inappropriately cozy relationship between Biogen and the FDA.

In addition to Acting Commissioner Woodcock’s call for an investigation, a similar request was made by two powerful U.S. House of Representatives committee chairs late last month, who called for a look at both the approval process and the drug’s expected cost, which could be as high as $56,000 per year per patient.

Representatives Carolyn B. Maloney, Chairwoman of the House Committee on Oversight and Reform, and Frank Pallone, Jr., Chairman of the House Energy and Commerce Committee, indicated both their committees will launch investigations into Aduhelm’s approval.

“We have serious concerns about the steep price of Biogen’s new Alzheimer’s drug Aduhelm and the process that led to its approval despite questions about the drug’s clinical benefit,” the two wrote in a June 25 press release. “We strongly support innovative treatments to help the millions of Americans who suffer from Alzheimer’s disease, but Aduhelm’s approval and its $56,000 annual price tag will have broader implications for seniors, providers, and taxpayers that warrant closer examination.”

Woodcock, in calling for an independent investigation by the Office of the Inspector General, said such action was necessary to protect the public’s confidence in the agency’s decision making process.

“To the extent these concerns could undermine the public’s confidence in FDA’s decisions, I believe that it is critical that the events at issue be reviewed by an independent body such as the Office of the Inspector General in order to determine whether any interactions that occurred between Biogen and FDA review staff were inconsistent with FDA policies and procedures,” she wrote.

Biogen officials have said they intend to cooperate with any and all investigations.