Long-Term Gantenerumab May Slow Decline in Dominantly Inherited Alzheimer Disease

TUESDAY, March 25, 2025 (HealthDay News) — For individuals with dominantly inherited Alzheimer disease (DIAD), long-term treatment with gantenerumab, an anti-amyloid beta antibody, may delay clinical decline, according to a study published in the April issue of The Lancet Neurology.

Randall J. Bateman, M.D., from Washington University School of Medicine in St. Louis, and colleagues conducted a three-year open-label extension (OLE) study to examine the safety and efficacy of long-term treatment with high-dose gantenerumab. The study was conducted at 18 sites and enrolled 73 individuals at risk for DIAD, who had participated in a phase 2/3 multiarm trial (DIAN-TU-001) and had known mutation status. The study was stopped early after a prespecified interim analysis due to lack of a regulatory path for gantenerumab. The primary outcome for the final analysis was the amyloid plaque measure ¹¹C-Pittsburgh compound-B positron emission tomography (PiB-PET) standardized uptake value ratio (SUVR [PiB-PET SUVR]) assessed in the modified intention-to-treat group at three years.

The researchers found that 47 participants stopped dosing due to early study termination and 13 discontinued prematurely for other reasons. At the interim analysis, in asymptomatic mutation carriers, the hazard ratio for clinical decline in the Clinical Dementia Rating-Sum of Boxes was 0.79 for participants treated with gantenerumab in either the double-blind or OLE period (95 percent confidence interval, 0.47 to 1.32) and 0.53 for those treated with gantenerumab the longest (95 percent confidence interval, 0.27 to 1.03). The adjusted mean change from OLE baseline to year 3 in PiB-PET SUVR was −0.71 SUVR at the final analysis.

“I am highly optimistic now, as this could be the first clinical evidence of what will become preventions for people at risk for Alzheimer”s disease,” Bateman said in a statement.

Several authors disclosed ties to biopharmaceutical companies, including F. Hoffmann-La Roche/Genentech, which is developing gantenerumab.

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