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Misleading Surrogate Evidence for FDA’s Aduhelm Approval

Amsterdam, NL – Last year, the FDA gave accelerated approval of the antibody aducanumab (marketed as Aduhelm by Biogen) for the treatment of Alzheimer’s disease. The approval was based solely on a presumed reduction in the amount of the protein “amyloid” in the brain as assessed by amyloid-PET scans and without evidence of significant clinical effect.

In a Commentary published in the Journal of Alzheimer’s Disease, authors Poul F. Høilund-Carlsen, Mona-Elisabeth Revheim, Abass Alavi, Nagichettiar Satyamurthy, and Jorge R. Barrio have detailed their views questioning the amyloid hypothesis that has dominated Alzheimer research and treatment trials for 30 years. In particular they question the use of amyloid-PET scanning, an imaging procedure that has been used to show whether new therapies are able to reduce cerebral amyloid deposits as this is assumed to inhibit the development of Alzheimer's disease. They contend that this very finding contributed to the FDA’s approval of Aduhelm contrary to its own independent expert panel which looked in vain for evidence of a favorable clinical effect. 

“We believe this kind of PET scanning is questionable and has misled the FDA into making a decision contrary to the agency's foremost mission to "protect and promote the public health," commented author Abass Alavi, MD, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. "Background for the approval is a never proven ‘amyloid hypothesis’ suggesting that Alzheimer’s disease is caused by cerebral amyloid deposits. Instead of reducing the amount of amyloid in the brain, we fear that Aduhelm and similar drugs cause increased brain damage.”

Dr. Alavi continued, “In addition to our concerns, we suspect that the amyloid PET scans performed are not reflecting amyloid removal, but rather are indicative of increased therapy-induced brain damage. We, therefore, strongly recommend that the FDA puts its Aduhelm approval on hold and requires thorough investigation of our presumption before taking a position on any further Alzheimer immunotherapy applications.”

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“Commentary: Amyloid PET: A Questionable Single Primary Surrogate Efficacy Measure on Alzheimer Immunotherapy Trials,” by Poul F. Høilund-Carlsen, Mona-Elisabeth Revheim, Abass Alavi , Nagichettiar Satyamurthy, and Jorge R. Barrio (, which is published in the Journal of Alzheimer’s Disease. It is openly available at

For further information contact Diana Murray, IOS Press, +1 718-640-5678 or To reach the authors please contact Abass Alavi, MD, at +1 215-662-3069 or

Now in its 25th year of publication, the Journal of Alzheimer's Disease (JAD) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment, and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease, and clinical trial outcomes. JAD has a Journal Impact Factor of 4.106 according to Journal Citation Reports™ (Clarivate, 2022). 

IOS Press is an independent international scientific, technical, medical (STM) publishing house established in 1987 in Amsterdam. We produce around 90 journals and 70 books annually in a broad range of subject categories, primarily specializing in biomedical and life sciences (including neurosciences, medical informatics, cancer research, rehabilitation) and physical sciences (including computer sciences, artificial intelligence, engineering). In addition, we offer specialized services that support scientific advancement.