Letter to the FDA Commissioner Requesting an Investigation of the Conduct of Alzheimer’s Disease Trials
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Public Citizen requested a formal investigation of the conduct of clinical trials of two recently approved drugs for Alzheimer’s disease, lecanemab (Leqembi) and donanemab (Kisunla), and the actions of the institutional review boards with oversight over these studies.
View the first statement from Public Citizen
December 13, 2024
Robert M. Califf, M.D.
Commissioner
Food and Drug Administration
U.S. Department of Health and Human Services
10903 New Hampshire Avenue
Silver Spring, MD 20993
Via e-mail: Commissioner_Writein@fda.gov; Elizabeth.Jungman@fda.hhs.gov
Re: Conduct of the Alzheimer’s Disease Trials for Lecanemab and Donanemab and the Actions of the Institutional Review Boards with Oversight Over These Studies
Dear Commissioner Califf:
Public Citizen, a consumer advocacy organization with more than 500,000 members and supporters nationwide, requests that the Food and Drug Administration (FDA) promptly launch a formal investigation into the conduct of two clinical trials for recently approved drugs for Alzheimer’s disease and the actions of the institutional review boards (IRBs) that had oversight over these studies.
Based on the reporting detailed in a New York Times article,[1] participants in clinical trials of two drugs for Alzheimer’s disease, lecanemab (Leqembi) and donanemab (Kisunla), were not informed whether their genetic profiles increased their risks of brain injuries from receiving the drugs. Instead, “volunteers first had to sign consent forms that said people with certain genetic profiles faced higher risks of brain injuries from receiving the drugs, and that participants would be tested for them — but not told the results.”
According to the New York Times investigation, the sponsor of lecanemab even specified in its trial protocol that “[n]o less than 70 percent” of enrolled subjects should have the APOE4 gene, the genetic profile that puts patients at a higher risk of developing Alzheimer’s disease.[2] Those who have two copies of this gene are at an especially increased risk for brain injuries when treated with drugs targeting amyloid beta, such as lecanemab.[3]
The New York Times article stated that this secrecy provision may have been put in place because “trial participants who are informed of their genetic profiles may skew their self-assessments of progress.” [4] More importantly, as Public Citizen said in a statement calling for federal officials to investigate the conduct in these trials, “[i]f subjects had known that they were at higher risk of brain injuries, they might have decided not to participate in the trials.”[5]
According to the FDA,[6] “[t]he purpose of IRB review is to assure, both in advance and by periodic review, that appropriate steps are taken to protect the rights and welfare of humans participating as subjects in the research. To accomplish this purpose, IRBs use a group process to review research protocols and related materials (e.g., informed consent documents and investigator brochures) to ensure protection of the rights and welfare of human subjects of research.”
Yet, the secrecy provisions were approved by the institutional review boards that had oversight over these studies, although they clearly disregarded a fundamental principle of informed consent and failed to adequately protect research subjects.
We therefore urge the FDA to promptly launch a formal investigation into the conduct and oversight of these clinical studies. The investigations should determine whether similar secrecy provisions are in place for ongoing or planned clinical trials to support new drug applications for Alzheimer’s disease drugs.
We hope you share our concern about this troubling matter and look forward to a favorable response to our request.
Sincerely,
Nina Zeldes, Ph.D.
Health Researcher
Public Citizen’s Health Research Group
Robert Steinbrook, M.D.
Director
Public Citizen’s Health Research Group
[1] The New York Times. What drugmakers did not tell volunteers in Alzheimer’s trials. October 23, 2024. https://www.nytimes.com/2024/10/23/health/alzheimers-drug-brain-bleeding.html. Accessed December 12, 2024.
[2] National Institute on Aging. Alzheimer’s disease genetics fact sheet. Last reviewed March 1, 2023. https://www.nia.nih.gov/health/genetics-and-family-history/alzheimers-disease-genetics-fact-sheet. Accessed December 12, 2024.
[3] Eisai. Label: lecanemab-irmb (LEQEMBI). November 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761269s008lbl.pdf. Accessed December 12, 2024.
[4] The New York Times. What drugmakers did not tell volunteers in Alzheimer’s trials. October 23, 2024. https://www.nytimes.com/2024/10/23/health/alzheimers-drug-brain-bleeding.html. Accessed December 12, 2024.
[5] Public Citizen. Federal officials should investigate conduct of Alzheimer’s disease trial. October 23, 2024. https://www.citizen.org/news/federal-officials-should-investigate-conduct-of-alzheimers-disease-trials/. Accessed December 12, 2024.
[6] Food and Drug Administration. Institutional Review Boards frequently asked questions. April 18, 2019. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/institutional-review-boards-frequently-asked-questions. Accessed December 12, 2024.