Gantenerumab treatment increases plasma beta‐amyloid(1–42) and decreases plasma pTau

Background Gantenerumab, a human monoclonal antibody targeting aggregated beta‐amyloid (Abeta), is a potential disease‐modifying treatment for early (prodromal‐to‐mild) Alzheimer’s disease (AD). SCarlet RoAD (NCT01224106) and Marguerite RoAD (NCT02051608) were two Phase III trials which assessed the efficacy and safety of subcutaneous, low‐dose gantenerumab in participants with prodromal and mild AD, respectively, for up to 2 years. Following a gap period gantenerumab treatment was continued with uptitration to a dose of 1,200 mg monthly in open‐label extensions (OLE), which demonstrated substantial Abeta removal by positron emission tomography without new or unexpected safety findings. The aim of this work is to investigate the pharmacodynamic effects of gantenerumab on plasma markers for amyloid and tau during both double‐blind and OLE periods. Method We evaluated the pharmacodynamic effects of subcutaneous gantenerumab on blood‐based biomarkers for amyloid and tau proteins in plasma samples collected once every year from participants who completed the double‐blind periods of SCarlet RoAD and Marguerite RoAD and participated in the OLE for up to 3 years. We measured Abeta(1–42) and phosphorylated Tau (pTau) in plasma samples using prototype Elecsys® immunoassays from Roche Diagnostics. Result Plasma Abeta(1–42) increases by 106% (95% confidence interval [CI]: 48% to 163%) in SCarlet RoAD and 63% (95% CI: 49% to 77%) in Marguerite RoAD after 3 years of OLE treatment. Plasma pTau decreases by 24% (95% CI: –44% to –4%) in SCarlet RoAD and 11% (95% CI: –23% to +2%) in Marguerite RoAD after 3 years of OLE treatment. Conclusion Chronic treatment with 1,200 mg subcutaneous injections of gantenerumab every 4 weeks increases levels of plasma Abeta(1–42) and decreases levels of plasma pTau consistently across both studies.