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AD/PD 2023 | Why have anti-amyloid monoclonal antibodies performed differently in Phase III trials

Stephen P. Salloway, MD, MS, Butler Hospital & Warren Alpert Medical School of Brown University, Providence, RI, discusses possible reasons for the differences in outcome between the GRADUATE I (NCT03444870) and GRADUATE II (NCT03443973) studies of gantenerumab and trials that have investigated lecanemab and aducanumab. Mainly highlighted by Prof. Salloway is the degree of amyloid lowering, which was substantially lower than predicted. The reason for this is unclear but could be down to the subcutaneous administration of gantenerumab, compared to intravenous lecanemab and aducanumab. It is known from results of the lecanemab, donanemab and aducanumab trials that a certain degree of amyloid lowering is needed in patients to see a clinical benefit, but cut-offs are yet to be determined. This interview took place at the AD/PD™ 2023 congress in Gothenburg, Sweden.

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