Lawmakers Demand FDA Documents on Aduhelm Approval

Two powerful U.S. House of Representative committee chairs are demanding federal drug regulators turn over records detailing the approval process for the controversial Alzheimer’s drug, Aduhelm, seeking answers about why the medication was allowed on the market over objections raised by health experts and scientists.

On September 1, Rep. Frank Pallone, Jr., chairman of the House Committee on Energy and Commerce, and Carolyn B. Maloney, chairwoman of the House Committee on Oversight and Reform, sent a letter (PDF) to Janet Woodcock, acting commissioner of the U.S. Food and Drug Administration (FDA), which requests the agency turn over numerous documents detailing its process in approving Aduhelm.

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. 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.

“We are concerned by apparent anomalies in FDA’s processes surrounding its review of Aduhelm,” the lawmakers wrote. “FDA granted accelerated approval for the drug despite concerns raised by experts – including the agency’s own staff and members of the FDA’s Peripheral and Central Nervous Systems Drugs Advisory Committee (PCNS Advisory Committee) – about the drug’s clinical benefit and the use of the accelerated approval pathway for Aduhelm. We are also concerned by reports of unusual coordination between FDA and Biogen throughout the drug’s approval process.”

Woodcock herself sent a letter to the FDA’s Inspector General in July, calling for an investigation into Aduhelm’s approval. She said such an investigation was warranted given the high amount of criticism the FDA faces over the drug’s approval. She also briefed the staffs of both House committees that same month, but Pallone and Maloney say the briefing left many questions unanswered.

The letter notes that the three members who resigned from the PCNS Advisory Committee made scathing comments which made why they were resigning clear. One said he was quitting because he did not “wish to be part of a sham process.” Another called Aduhelm “probably the worst drug approval decision in recent U.S. history.”

The approval has also led to mistrust in the medical industry, resulting in several major medical centers vowing not to use the drug, including the Cleveland Clinic and the Department of Veterans Affairs.

The two House chairs say they want the FDA to turn over a number of key documents by September 16, 2021. They request the FDA to describe what body of evidence the FDA relied on to approve the drug, after its own advisory committee looked at the clinical trial data and resolutely said Aduhelm should not be approved. They want data on when the FDA decided to look at accelerated approval, how the agency reconciles its decision versus the opinions of so many experts and scientists, how the FDA chose the questions it asked of its advisory committee, and what steps, if any, the FDA took to further evaluate Aduhelm following the rejection of the committee.

The letter also requests the FDA describe any communications between the agency and Biogen and why it jointly co-authored a primary briefing document for the committee with Biogen.

There are several pages of such questions for the FDA and requests for data detailed in the letter.

Aduhelm Advisory Committee Votes

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 PCNS 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.