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Chairs Pallone and Maloney Request Answers from FDA on the Approval Process for Alzheimer’s Drug Aduhelm

Sep 2, 2021
Press Release
“We are concerned by apparent anomalies in FDA’s processes surrounding its review of Aduhelm”

Energy and Commerce Chairman Frank Pallone, Jr. (D-NJ) and Oversight and Reform Chairwoman Carolyn B. Maloney (D-NY) sent a letter to Food and Drug Administration (FDA) Acting Commissioner Dr. Janet Woodcock seeking information regarding the review process and accelerated approval of Biogen Inc.’s Alzheimer’s drug, Aduhelm. The letter to FDA follows a previous letter to Biogen in July and is part of the committees’ ongoing investigation into the drug’s approval process, marketing, and pricing.

“We are concerned by apparent anomalies in FDA’s processes surrounding its review of Aduhelm,” the Chairs wrote. “FDA granted accelerated approval for the drug despite concerns raised by experts — including the agency’s own staff and members of 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.”

The Chairs noted that FDA and Biogen have relied on claims that a post hoc analysis of cancelled clinical trials showed that the drug successfully reduces amyloid beta plaque in the brain. However, the link between reduction of amyloid beta plaque and the slowing of cognitive decline in Alzheimer’s patients is not well-established and has been questioned by numerous experts. Prior to Aduhelm’s approval, FDA itself did not consider the reduction of amyloid beta plaque to be a surrogate endpoint likely to result in clinical benefit, raising additional questions about the drug’s approval process. 

Following FDA’s June 7, 2021, announcement granting accelerated approval of Aduhelm, three PCNS Advisory Committee members resigned in protest, with one member calling it “probably the worst drug approval decision in recent U.S. history.” Since then, major medical centers such as the Cleveland Clinic and Mount Sinai have decided not to administer Aduhelm to their patients, large health insurers have declined to cover the drug, and the Department of Veterans Affairs (VA) has declined to add the drug to the VA National Formulary, citing the known risk of significant adverse events and the lack of evidence of a positive impact on cognition.

“Aduhelm’s approval has far-reaching implications, not only for individuals with Alzheimer’s, but also for seniors, federal health care programs, and future research, development, and approval of drugs for Alzheimer’s and other diseases,” Pallone and Maloney concluded in their letter. “To help ensure that the American people continue to have the utmost confidence in FDA and the safety and efficacy of approved drugs, and to help inform future legislation, we need more information about FDA’s process for reviewing and approving Aduhelm.”

In the letter, Pallone and Maloney also raised concerns about reports of atypical coordination between FDA and Biogen throughout the drug’s approval process, and indications that interactions between FDA and Biogen may have been contrary to FDA’s own guidance for staff engagement with sponsors during drug development. In July, FDA requested that the Department of Health and Human Services Office of the Inspector General (HHS OIG) investigate the interactions between FDA and Biogen, and in August, the HHS OIG announced it would review FDA’s interactions with outside entities as well as how “FDA implements the accelerated approval pathway.” 

While the Chairs commended these efforts to improve transparency, they also  emphasized that clarity is needed now, and the American people—particularly Alzheimer’s patients and their caregivers—cannot wait until the OIG report is expected to be completed in 2023.

The Chairs requested that FDA provide key information to the committees by September 16, 2021, including:

  • An explanation of how FDA reconciles its determination that Aduhelm met the criteria for accelerated approval with the views of the PCNS Advisory Committee, internal experts from FDA’s Office of Biostatistics, and some of the nation’s largest medical centers and insurers, all of whom have determined that there is insufficient data on the safety and efficacy of Aduhelm;
  • FDA’s process or related policies in place for making an approval determination when there is FDA staff disagreement with the relevant Advisory Committee and/or when there is internal disagreement among the relevant FDA expert reviewers, including information on whether Aduhelm’s approval deviated from this process and these policies;
  • Details of when FDA first discussed the potential use of the accelerated approval pathway for Aduhelm internally and with Biogen and who was a part of such discussions;
  • Documents related to any internal agency reviews or assessments concerning interactions between FDA personnel and Biogen related to the approval of Aduhelm;
  • FDA’s internal discussions and process for approving Aduhelm for a broader treatment indication than what was studied in the clinical trials and for updating Aduhelm’s label post-approval; and
  • A list of all formal and informal conversations and meetings between FDA and any representative of Biogen and all documents, including communications, related to those conversations since January 2018, as well as an explanation for why any such meetings were not memorialized in keeping with FDA best practices.

Read the full letter HERE.